Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal

Antonio Ayala, Mario F Muñoz, Sandro Argüelles, Antonio Ayala, Mario F Muñoz, Sandro Argüelles

Abstract

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970-1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010-2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

Figures

Figure 1
Figure 1
Fenton and Haber-Weiss reaction. Reduced form of transition-metals (Mn) reacts trough the Fenton reaction with hydrogen peroxide (H2O2), leading to the generation of •OH. Superoxide radical (O2 •−) can also react with oxidized form of transition metals (M(n+1)) in the Haber-Weiss reaction leading to the production of Mn, which then again affects redox cycling.
Figure 2
Figure 2
Lipid peroxidation process. In Initiation, prooxidants abstract the allylic hydrogen forming the carbon-centered lipid radical; the carbon radical tends to be stabilized by a molecular rearrangement to form a conjugated diene (step 1). In the propagation phase, lipid radical rapidly reacts with oxygen to form a lipid peroxy radical (step 2) which abstracts a hydrogen from another lipid molecule generating a new lipid radical and lipid hydroperoxide (step 3). In the termination reaction, antioxidants donate a hydrogen atom to the lipid peroxy radical species resulting in the formation of nonradical products (step 4).
Figure 3
Figure 3
MDA formation and metabolism. MDA can be generated in vivo by decomposition of arachidonic acid (AA) and larger PUFAs as a side product by enzymatic processes during the biosynthesis of thromboxane A2 (TXA2) and 12-l-hydroxy-5,8,10-heptadecatrienoic acid (HHT) (blue pathway), or through nonenzymatic processes by bicyclic endoperoxides produced during lipid peroxidation (red pathway). One formed MDA can be enzymatically metabolized (green pathway). Key enzymes involved in the formation and metabolism of MDA: cyclooxygenases (1), prostacyclin hydroperoxidase (2), thromboxane synthase (3), aldehyde dehydrogenase (4), decarboxylase (5), acetyl CoA synthase (6), and tricarboxylic acid cycle (7).
Figure 4
Figure 4
Enzymatic production of 4-HNE and metabolism. In plant enzymatic route to 4-HNE includes lipoxygenase (LOX), -hydroperoxide lyase (HPL), alkenal oxygenase (AKO), and peroxygenases. 4-HNE metabolism may lead to the formation of corresponding alcohol 1,4-dihydroxy-2-nonene (DHN), corresponding acid 4-hydroxy-2-nonenoic acid (HNA), and HNE–glutathione conjugate products. 4-HNE conjugation with glutathione s-transferase (GSH) produce glutathionyl-HNE (GS-HNE) followed by NADH-dependent alcohol dehydrogenase (ADH-)catalysed reduction to glutathionyl-DNH (GS-DNH) and/or aldehyde dehydrogenase (ALDH-)catalysed oxidation to glutathionyl-HNA (GS-HNA). 4-HNE is metabolized by ALDH yielding HNA, which is metabolized by cytochrome P450 (CYP) to form 9-hydroxy-HNA (9-OH-HNA). 4-HNE may be also metabolized by ADH to produce DNH.
Figure 5
Figure 5
Nonenzymatic 4-HNE production. Initial abstraction of bisallylic hydrogen of lipoic acid (LA) produces fatty radicals. 4-HNE formation starting with 9- and 13-hydroperoxyoctadecadienoate (HPODE) (red and blue pathways, resp.). 4-HNE is generated by beta-scission of a hydroxyalkoxy radical that is produced after cyclization of alkoxy radical in the presence of transition metal ions and two molecules of oxygen; this reaction involves hydrogen abstraction (1). Peroxy radical cyclizes to form a dioxetane which is oxygenated to peroxy-dioxetane that is fragmented and after two hydrogen abstractions produce 4-HNE (2). Hydroperoxyl radical is oxygenated to dioxetane that is further fragmented to produce 4-hydroperoxy-2E-nonenal (4-HPNE), an immediate precursor of 4-HNE (3). Bicyclic endoperoxides react with reduced form of transition metal, such as iron (Fe2+) to produce alkoxyl radicals which after reaction with oxygen (O2), hydrogen abstraction (H+), and fragmentation produce 4-HNE (4). Alkoxyl radical after cyclization, oxygenation, hydrogen abstraction, oxidation of transition metal, hydrolysis, and rearrangement yields 4-HNE (5). With arachidonic acid, 11- and 15- hydroperoxyeicosatetraenoic acids (HPETE) are the precursors to form 4-HNE via the analogous mechanisms.
Figure 6
Figure 6
4-HNE promotes cell survival or induces cell death. Depending on cell type, damage/repair capacities and cellular metabolic circumstances 4-HNE can promote cell survival or induce cell death. 4-HNE at physiological levels is enzymatically metabolized and at low levels plays an important role as signaling molecule stimulating gene expression, enhance cellular antioxidant capacity and exert adaptive response; at medium levels organelle and protein damage lead to induction of autophagy, senescence, or cell cycle arrest and at high or very high levels promote adducts formation and apoptosis or necrosis cell death, respectively.
Figure 7
Figure 7
Mechanisms showing how cumene hydroperoxide produces lipophilic cumoxyl and cumoperoxyl radicals. Cumene hydroperoxide in presence of transition metal ions produces cumoxyl radical (step 1), which abstracts a hydrogen (H) from a lipid (PUFA) molecule (LH) generating cumyl alcohol and lipid radical (L•) that reacts readily with oxygen promoting the initiation or propagation of lipid peroxidation. (Step 2). Cumoxyl radical can also react with other cumene hydroperoxide molecules to yield cumyl alcohol and cumoperoxyl radical (step 3). Finally, cumoperoxil radical may abstract hydrogen (H) from the closest available lipid to produce a new cumene hydroperoxide and lipid radical (L•) which then again affects lipid peroxidation cycling (step 4). Cumoperoxyl radical may also react with oxygen to yield a new cumoxyl radical thus initiating a chain reaction (step 5).

References

    1. Frühbeck G, Gómez-Ambrosi J, Muruzábal FJ, Burrell MA. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. The American Journal of Physiology: Endocrinology and Metabolism. 2001;280(6):E827–E847.
    1. Frayn KN. Regulation of fatty acid delivery in vivo. Advances in Experimental Medicine and Biology. 1998;441:171–179.
    1. Vance E, Vance JE. Biochemistry: Biochemistry of Lipids, Lipoproteins and Membranes. 4th edition 2002.
    1. Massey KA, Nicolaou A. Lipidomics of polyunsaturated-fatty-acid-derived oxygenated metabolites. Biochemical Society Transactions. 2011;39(5):1240–1246.
    1. Massey KA, Nicolaou A. Lipidomics of oxidized polyunsaturated fatty acids. Free Radical Biology and Medicine. 2013;59:45–55.
    1. Jornayvaz FR, Shulman GI. Diacylglycerol activation of protein kinase Cε and hepatic insulin resistance. Cell Metabolism. 2012;15(5):574–584.
    1. Giorgi C, Agnoletto C, Baldini C, et al. Redox control of protein kinase C: cell-and disease-specific aspects. Antioxidants and Redox Signaling. 2010;13(7):1051–1085.
    1. Yang C, Kazanietz MG. Chimaerins: GAPs that bridge diacylglycerol signalling and the small G-protein Rac. Biochemical Journal. 2007;403(1):1–12.
    1. Baumann J, Sevinsky C, Conklin DS. Lipid biology of breast cancer. Biochimica et Biophysica Acta. 2013;1831(10):1509–1517.
    1. Fisher SK, Novak JE, Agranoff BW. Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. Journal of Neurochemistry. 2002;82(4):736–754.
    1. Conway SJ, Miller GJ. Biology-enabling inositol phosphates, phosphatidylinositol phosphates and derivatives. Natural Product Reports. 2007;24(4):687–707.
    1. Takuwa Y, Okamoto Y, Yoshioka K, Takuwa N. Sphingosine-1-phosphate signaling in physiology and diseases. BioFactors. 2012;38(5):329–337.
    1. Mattson MP. Membrane Lipid Signaling in Aging and Age-Related Disease. Elsevier; 2003.
    1. Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nature Reviews Molecular Cell Biology. 2008;9(2):139–150.
    1. Aoki T, Narumiya S. Prostaglandins and chronic inflammation. Trends in Pharmacological Sciences. 2012;33(6):304–311.
    1. Tang EHC, Libby P, Vanhoutte PM, Xu A. Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases. Journal of Cardiovascular Pharmacology. 2012;59(2):116–123.
    1. Kalinski P. Regulation of immune responses by prostaglandin E2 . Journal of Immunology. 2012;188(1):21–28.
    1. Kay JG, Grinstein S. Phosphatidylserine-mediated cellular signaling. Advances in Experimental Medicine and Biology. 2013;991:177–193.
    1. Pluchino N, Russo M, Santoro AN, Litta P, Cela V, Genazzani AR. Steroid hormones and BDNF. Neuroscience. 2013;239:271–279.
    1. Moldovan L, Moldovan NI. Oxygen free radicals and redox biology of organelles. Histochemistry and Cell Biology. 2004;122(4):395–412.
    1. Lane N. Oxygen: The Molecule that Made the World. Oxford University Press; 2002.
    1. Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal. 1984;219(1):1–14.
    1. Venero JL, Revuelta M, Atiki L, et al. Evidence for dopamine-derived hydroxyl radical formation in the nigrostriatal system in response to axotomy. Free Radical Biology and Medicine. 2003;34(1):111–123.
    1. Castellani RJ, Honda K, Zhu X, et al. Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease. Ageing Research Reviews. 2004;3(3):319–326.
    1. Lipinski B, Pretorius E. Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron. Hematology. 2012;17(4):241–247.
    1. Dizdaroglu M, Jaruga P. Mechanisms of free radical-induced damage to DNA. Free Radical Research. 2012;46(4):382–419.
    1. Kanno T, Nakamura K, Ikai H, Kikuchi K, Sasaki K, Niwano Y. Literature review of the role of hydroxyl radicals in chemically-induced mutagenicity and carcinogenicity for the risk assessment of a disinfection system utilizing photolysis of hydrogen peroxide. Journal of Clinical Biochemistry and Nutrition. 2012;51(1):9–14.
    1. Bielski BHJ, Arudi RL, Sutherland MW. A study of the reactivity of HO2/O2- with unsaturated fatty acids. Journal of Biological Chemistry. 1983;258(8):4759–4761.
    1. Schneider C, Boeglin WE, Yin H, Porter NA, Brash AR. Intermolecular peroxyl radical reactions during autoxidation of hydroxy and hydroperoxy arachidonic acids generate a novel series of epoxidized products. Chemical Research in Toxicology. 2008;21(4):895–903.
    1. Browne RW, Armstrong D. HPLC analysis of lipid-derived polyunsaturated fatty acid peroxidation products in oxidatively modified human plasma. Clinical Chemistry. 2000;46(6, part 1):829–836.
    1. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chemical Reviews. 2011;111(10):5944–5972.
    1. Volinsky R, Kinnunen PKJ. Oxidized phosphatidylcholines in membrane-level cellular signaling: from biophysics to physiology and molecular pathology. FEBS Journal. 2013;280(12):2806–2816.
    1. Kinnunen PKJ, Kaarniranta K, Mahalka AK. Protein-oxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations. Biochimica et Biophysica Acta. 2012;1818(10):2446–2455.
    1. Reis A, Spickett CM. Chemistry of phospholipid oxidation. Biochimica et Biophysica Acta. 2012;1818(10):2374–2387.
    1. Fruhwirth GO, Loidl A, Hermetter A. Oxidized phospholipids: from molecular properties to disease. Biochimica et Biophysica Acta: Molecular Basis of Disease. 2007;1772(7):718–736.
    1. Girotti AW. Lipid hydroperoxide generation, turnover, and effector action in biological systems. Journal of Lipid Research. 1998;39(8):1529–1542.
    1. Kanner J, German JB, Kinsella JE. Initiation of lipid peroxidation in biological systems. Critical Reviews in Food Science and Nutrition. 1987;25(4):317–364.
    1. Esterbauer H, Cheeseman KH, Dianzani MU. Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes. Biochemical Journal. 1982;208(1):129–140.
    1. Poli G, Dianzani MU, Cheeseman KH, Slater TF, Lang J, Esterbauer H. Separation and characterization of the aldehydic products of lipid peroxidation stimulated by carbon tetrachloride or ADP-iron in isolated rat hepatocytes and rat liver microsomal suspensions. Biochemical Journal. 1985;227(2):629–638.
    1. Benedetti A, Comporti M, Esterbauer H. Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochimica et Biophysica Acta. 1980;620(2):281–296.
    1. Cadenas E, Müller A, Brigelius R, Esterbauer H, Sies H. Effects of 4-hydroxynonenal on isolated hepatocytes. Studies on chemiluminescence response, alkane production and glutathione status. Biochemical Journal. 1983;214(2):479–487.
    1. Esterbauer H, Lang J, Zadravec S, Slater TF. Detection of malonaldehyde by high-performance liquid chromatography. Methods in Enzymology. 1984;105:319–328.
    1. Winkler P, Lindner W, Esterbauer H, Schauenstein E, Schaur RJ, Khoschsorur GA. Detection of 4-hydroxynonenal as a product of lipid peroxidation in native Ehrlich ascites tumor cells. Biochimica et Biophysica Acta: Lipids and Lipid Metabolism. 1984;796(3):232–237.
    1. Esterbauer H, Benedetti A, Lang J, Fulceri R, Fauler G, Comporti M. Studies on the mechanism of formation of 4-hydroxynonenal during microsomal lipid peroxidation. Biochimica et Biophysica Acta: Lipids and Lipid Metabolism. 1986;876(1):154–166.
    1. Hurst JS, Slater TF, Lang J. Effects of the lipid peroxidation product 4-hydroxynonenal on the aggregation of human platelets. Chemico-Biological Interactions. 1987;61(2):109–124.
    1. Cheeseman KH, Beavis A, Esterbauer H. Hydroxyl-radical-induced iron-catalysed degradation of 2-deoxyribose. Quantitative determination of malondialdehyde. Biochemical Journal. 1988;252(3):649–653.
    1. Esterbauer H, Zolliner H. Methods for determination of aldehydic lipid peroxidation products. Free Radical Biology and Medicine. 1989;7(2):197–203.
    1. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods in Enzymology. 1990;186:407–421.
    1. Esterbauer H, Schaur RJ, Zollner H. Chemistry and Biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology and Medicine. 1991;11(1):81–128.
    1. Esterbauer H, Eckl P, Ortner A. Possible mutagens derived from lipids and lipid precursors. Mutation Research. 1990;238(3):223–233.
    1. Pryor WA. On the detection of lipid hydroperoxides in biological samples. Free Radical Biology and Medicine. 1989;7(2):177–178.
    1. Sinnhuber RO, Yu TC, Yu TC. Characterization of the red pigment formed in the 2-thiobarbituric acid determination of oxidative rancidity. Journal of Food Science. 1958;23(6):626–634.
    1. Giera M, Lingeman H, Niessen WMA. Recent advancements in the LC- and GC-based analysis of malondialdehyde (MDA): a brief overview. Chromatographia. 2012;75(9-10):433–440.
    1. Schauenstein E. Autoxidation of polyunsaturated esters in water: chemical structure and biological activity of the products. Journal of Lipid Research. 1967;8(5):417–428.
    1. Brambilla G, Sciabà L, Faggin P, et al. Cytotoxicity, DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes. Mutation Research. 1986;171(2-3):169–176.
    1. Schaur RJ. Basic aspects of the biochemical reactivity of 4-hydroxynonenal. Molecular Aspects of Medicine. 2003;24(4-5):149–159.
    1. Zarkovic N. 4-Hydroxynonenal as a bioactive marker of pathophysiological processes. Molecular Aspects of Medicine. 2003;24(4-5):281–291.
    1. Niki E. Biomarkers of lipid peroxidation in clinical material. Biochimica et Biophysica Acta. 2014;1840(2):809–817.
    1. Argüelles S, García S, Maldonado M, Machado A, Ayala A. Do the serum oxidative stress biomarkers provide a reasonable index of the general oxidative stress status? Biochimica et Biophysica Acta: General Subjects. 2004;1674(3):251–259.
    1. Argüelles S, Gómez A, Machado A, Ayala A. A preliminary analysis of within-subject variation in human serum oxidative stress parameters as a function of time. Rejuvenation Research. 2007;10(4):621–636.
    1. Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochimica et Biophysica Acta. 2013;1830(5):3289–3303.
    1. Steinbrenner H, Sies H. Protection against reactive oxygen species by selenoproteins. Biochimica et Biophysica Acta: General Subjects. 2009;1790(11):1478–1485.
    1. Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Current Medicinal Chemistry. 2005;12(10):1161–1208.
    1. Szabó C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nature Reviews Drug Discovery. 2007;6(8):662–680.
    1. Winterbourn CC. Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous acid. Toxicology. 2002;181-182:223–227.
    1. Malle E, Marsche G, Arnhold J, Davies MJ. Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids. 2006;1761(4):392–415.
    1. Miyamoto S, Ronsein GE, Prado FM, et al. Biological hydroperoxides and singlet molecular oxygen generation. IUBMB Life. 2007;59(4-5):322–331.
    1. Miyamoto S, Martinez GR, Rettori D, Augusto O, Medeiros MHG, Di Mascio P. Linoleic acid hydroperoxide reacts with hypochlorous acid, generating peroxyl radical intermediates and singlet molecular oxygen. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(2):293–298.
    1. Gracanin M, Hawkins CL, Pattison DI, Davies MJ. Singlet-oxygen-mediated amino acid and protein oxidation: formation of tryptophan peroxides and decomposition products. Free Radical Biology and Medicine. 2009;47(1):92–102.
    1. Davies MJ. Singlet oxygen-mediated damage to proteins and its consequences. Biochemical and Biophysical Research Communications. 2003;305(3):761–770.
    1. Domingues RM, Domingues P, Melo T, Pérez-Sala D, Reis A, Spickett CM. Lipoxidation adducts with peptides and proteins: deleterious modifications or signaling mechanisms? Journal of Proteomics. 2013;92:110–131.
    1. Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. British Journal of Pharmacology. 2008;153(1):6–20.
    1. Wang X, Lei XG, Wang J. Malondialdehyde regulates glucose-stimulated insulin secretion in murine islets via TCF7L2-dependent Wnt signaling pathway. Molecular and Cellular Endocrinology. 2014;382(1):8–16.
    1. García-Ruiz I, de la Torre P, Díaz T, et al. Sp1 and Sp3 transcription factors mediate malondialdehyde-induced collagen alpha 1(I) gene expression in cultured hepatic stellate cells. The Journal of Biological Chemistry. 2002;277(34):30551–30558.
    1. Li L, Davie JR. The role of Sp1 and Sp3 in normal and cancer cell biology. Annals of Anatomy: Anatomischer Anzeiger. 2010;192(5):275–283.
    1. Zarkovic N, Cipak A, Jaganjac M, Borovic S, Zarkovic K. Pathophysiological relevance of aldehydic protein modifications. Journal of Proteomics. 2013;92:239–247.
    1. Blair IA. DNA adducts with lipid peroxidation products. Journal of Biological Chemistry. 2008;283(23):15545–15549.
    1. Łuczaj W, Skrzydlewska E. DNA damage caused by lipid peroxidation products. Cellular and Molecular Biology Letters. 2003;8(2):391–413.
    1. Garcia SC, Grotto D, Bulcão RP, et al. Evaluation of lipid damage related to pathological and physiological conditions. Drug and Chemical Toxicology. 2013;36(3):306–312.
    1. Li G, Chen Y, Hu H, et al. Association between age-related decline of kidney function and plasma malondialdehyde. Rejuvenation Research. 2012;15(3):257–264.
    1. Sanyal J, Bandyopadhyay SK, Banerjee TK, et al. Plasma levels of lipid peroxides in patients with Parkinson’s disease. European Review for Medical and Pharmacological Sciences. 2009;13(2):129–132.
    1. Shanmugam N, Figarola JL, Li Y, Swiderski PM, Rahbar S, Natarajan R. Proinflammatory effects of advanced lipoxidation end products in monocytes. Diabetes. 2008;57(4):879–888.
    1. Baskol G, Demir H, Baskol M, et al. Investigation of protein oxidation and lipid peroxidation in patients with rheumatoid arthritis. Cell Biochemistry and Function. 2006;24(4):307–311.
    1. Merendino RA, Salvo F, Saija A, et al. Malondialdehyde in benign prostate hypertrophy: a useful marker? Mediators of Inflammation. 2003;12(2):127–128.
    1. Paggiaro PL, Bartoli ML, Novelli F, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators of Inflammation. 2011;2011:7 pages.891752
    1. Hecker M, Ullrich V. On the mechanism of prostacyclin and thromboxane A2 biosynthesis. Journal of Biological Chemistry. 1989;264(1):141–150.
    1. Sharma RA, Gescher A, Plastaras JP, et al. Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells. Carcinogenesis. 2001;22(9):1557–1560.
    1. Tsikas D, Suchy MT, Niemann J, et al. Glutathione promotes prostaglandin H synthase (cyclooxygenase)-dependent formation of malondialdehyde and 15(S)-8-iso-prostaglandin F2α . FEBS Letters. 2012;586(20):3723–3730.
    1. Griesser M, Boeglin WE, Suzuki T, Schneider C. Convergence of the 5-LOX and COX-2 pathways: heme-catalyzed cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde fragments. Journal of Lipid Research. 2009;50(12):2455–2462.
    1. Kadiiska MB, Gladen BC, Baird DD, et al. Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning. Free Radical Biology and Medicine. 2005;38(6):711–718.
    1. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(5):986–1000.
    1. Ekambaram P, Lambiv W, Cazzolli R, Ashton AW, Honn KV. The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis. Cancer and Metastasis Reviews. 2011;30(3-4):397–408.
    1. Yang H, Chen C. Cyclooxygenase-2 in synaptic signaling. Current Pharmaceutical Design. 2008;14(14):1443–1451.
    1. Pryor WA, Stanley JP, Blair E. Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA reactive materials from prostaglandin like endoperoxides. Lipids. 1976;11(5):370–379.
    1. Milne GL, Yin H, Morrow JD. Human biochemistry of the isoprostane pathway. Journal of Biological Chemistry. 2008;283(23):15533–15537.
    1. Gao L, Zackert WE, Hasford JJ, et al. Formation of prostaglandins E2 and D2 via the isoprostane pathway. A mechanism for the generation of bioactive prostaglandins independent of cyclooxygenase. Journal of Biological Chemistry. 2003;278(31):28479–28489.
    1. Yin H, Gao L, Tai H-H, Murphey LJ, Porter NA, Morrow JD. Urinary prostaglandin F2α is generated from the isoprostane pathway and not the cyclooxygenase in humans. Journal of Biological Chemistry. 2007;282(1):329–336.
    1. Brooks JD, Milne GL, Yin H, Sanchez SC, Porter NA, Morrow JD. Formation of highly reactive cyclopentenone isoprostane compounds (A 3/J3-isoprostanes) in vivo from eicosapentaenoic acid. Journal of Biological Chemistry. 2008;283(18):12043–12055.
    1. Roberts LJ, II, Fessel JP, Davies SS. The biochemistry of the isoprostane, neuroprostane, and isofuran pathways of lipid peroxidation. Brain Pathology. 2005;15(2):143–148.
    1. Onyango AN, Baba N. New hypotheses on the pathways of formation of malondialdehyde and isofurans. Free Radical Biology and Medicine. 2010;49(10):1594–1600.
    1. Siu GM, Draper HH. Metabolism of malonaldehyde in vivo and in vitro. Lipids. 1982;17(5):349–355.
    1. Marnett LJ, Buck J, Tuttle MA, Basu AK, Bull AW. Distribution and oxidation of malondialdehyde in mice. Prostaglandins. 1985;30(2):241–254.
    1. Agadjanyan ZS, Dmitriev LF, Dugin SF. A new role of phosphoglucose isomerase. Involvement of the glycolytic enzyme in aldehyde metabolism. Biochemistry. 2005;70(11):1251–1255.
    1. Pizzimenti S, Ciamporcero E, Daga M, et al. Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Frontiers in Physiology. 2013;4, article 242
    1. Skoumalová A, Hort J. Blood markers of oxidative stress in Alzheimer’s disease. Journal of Cellular and Molecular Medicine. 2012;16(10):2291–2300.
    1. Mangialasche F, Polidori MC, Monastero R, et al. Biomarkers of oxidative and nitrosative damage in Alzheimer’s disease and mild cognitive impairment. Ageing Research Reviews. 2009;8(4):285–305.
    1. Pamplona R, Dalfó E, Ayala V, et al. Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation: effects of Alzheimer disease and identification of lipoxidation targets. Journal of Biological Chemistry. 2005;280(22):21522–21530.
    1. Cristalli DO, Arnal N, Marra FA, De Alaniz MJT, Marra CA. Peripheral markers in neurodegenerative patients and their first-degree relatives. Journal of the Neurological Sciences. 2012;314(1-2):48–56.
    1. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology. 2007;39(1):44–84.
    1. López N, Tormo C, De Blas I, Llinares I, Alom J. Oxidative stress in Alzheimer’s disease and mild cognitive impairment with high sensitivity and specificity. Journal of Alzheimer's Disease. 2013;33(3):823–829.
    1. Torres LL, Quaglio NB, De Souza GT, et al. Peripheral oxidative stress biomarkers in mild cognitive impairment and alzheimer’s disease. Journal of Alzheimer’s Disease. 2011;26(1):59–68.
    1. Polidori MC, Mecocci P. Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease. Journal of Alzheimer’s Disease. 2002;4(6):517–522.
    1. Padurariu M, Ciobica A, Hritcu L, Stoica B, Bild W, Stefanescu C. Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neuroscience Letters. 2010;469(1):6–10.
    1. Sanders LH, Timothy Greenamyre J. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radical Biology and Medicine. 2013;62:111–120.
    1. Mythri RB, Venkateshappa C, Harish G, et al. Evaluation of Markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson’s disease brains. Neurochemical Research. 2011;36(8):1452–1463.
    1. Navarro A, Boveris A, Bández MJ, et al. Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies. Free Radical Biology and Medicine. 2009;46(12):1574–1580.
    1. Kilinç A, Yalçin AS, Yalçin D, Taga Y, Emerk K. Increased erythrocyte susceptibility to lipid peroxidation in human Parkinson’s disease. Neuroscience Letters. 1988;87(3):307–310.
    1. Baillet A, Chanteperdrix V, Trocmé C, Casez P, Garrel C, Besson G. The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson’s disease. Neurochemical Research. 2010;35(10):1530–1537.
    1. Chen CM, Liu JL, Wu YR, et al. Increased oxidative damage in peripheral blood correlates with severity of Parkinson’s disease. Neurobiology of Disease. 2009;33(3):429–435.
    1. Kalra J, Rajput AH, Mantha SV, Chaudhary AK, Prasad K. Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson’s disease. Molecular and Cellular Biochemistry. 1992;112(2):181–186.
    1. Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stress in Parkinson’s disease. European Neurology. 2007;58(2):78–83.
    1. Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ. Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells. Journal of Biological Chemistry. 2003;278(33):31426–31433.
    1. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutrition, Metabolism and Cardiovascular Diseases. 2005;15(4):316–328.
    1. VanderVeen LA, Hashim MF, Shyr Y, Marnett LJ. Induction of frameshift and base pair substitution mutations by the major DNA adduct of the endogenous carcinogen malondialdehyde. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(24):14247–14252.
    1. Peluso MEM, Munnia A, Bollati V, et al. Aberrant methylation of hypermethylated-in-cancer-1 and exocyclic DNA adducts in tobacco smokers. Toxicological Sciences. 2014;137(1):47–54.
    1. Cai F, Dupertuis YM, Pichard C. Role of polyunsaturated fatty acids and lipid peroxidation on colorectal cancer risk and treatments. Current Opinion in Clinical Nutrition and Metabolic Care. 2012;15(2):99–106.
    1. Nair U, Bartsch H, Nair J. Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans. Free Radical Biology and Medicine. 2007;43(8):1109–1120.
    1. Bartsch H, Nair J. Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers for chemoprevention of inflammation-driven malignancies. Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis. 2005;591(1-2):34–44.
    1. Wang M, Dhingra K, Hittelman WN, Liehr JG, De Andrade M, Li D. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiology Biomarkers and Prevention. 1996;5(9):705–710.
    1. Marnett LJ. Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment. Journal of Organic Chemistry. 2012;77(12):5224–5238.
    1. Dalleau S, Baradat M, Guéraud F, Huc L. Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance. Cell Death and Differentiation. 2013;20(12):1615–1630.
    1. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncology. 2012;2012:21 pages.137289
    1. Huang H, Kozekov ID, Kozekova A, et al. DNA cross-link induced by trans-4-hydroxynonenal. Environmental and Molecular Mutagenesis. 2010;51(6):625–634.
    1. Minko IG, Kozekov ID, Harris TM, Rizzo CJ, Lloyd RS, Stone MP. Chemistry and biology of DNA containing 1,N2-deoxyguanosine adducts of the α,β-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal. Chemical Research in Toxicology. 2009;22(5):759–778.
    1. Negre-Salvayre A, Auge N, Ayala V, et al. Pathological aspects of lipid peroxidation. Free Radical Research. 2010;44(10):1125–1171.
    1. Chung F-L, Pan J, Choudhury S, Roy R, Hu W, Tang M-S. Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from ω-3 and ω-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation. Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis. 2003;531(1-2):25–36.
    1. Lee R, Margaritis M, Channon KM, Antoniades C. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Current Medicinal Chemistry. 2012;19(16):2504–2520.
    1. Uchida K. Role of reactive aldehyde in cardiovascular diseases. Free Radical Biology and Medicine. 2000;28(12):1685–1696.
    1. Anderson EJ, Katunga LA, Willis MS. Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. Clinical and Experimental Pharmacology and Physiology. 2012;39(2):179–193.
    1. Nwose EU, Jelinek HF, Richards RS, Kerr RG. Erythrocyte oxidative stress in clinical management of diabetes and its cardiovascular complications. British Journal of Biomedical Science. 2007;64(1):35–43.
    1. Ho E, Karimi Galougahi K, Liu CC, Bhindi R, Figtree GA. Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox Biology. 2013;1(1):483–491.
    1. Chapple SJ, Cheng X, Mann GE. Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease. Redox Biology. 2013;1(1):319–331.
    1. Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Experimental Gerontology. 2009;44(10):625–633.
    1. Leonarduzzi G, Chiarpotto E, Biasi F, Poli G. 4-Hydroxynonenal and cholesterol oxidation products in atherosclerosis. Molecular Nutrition and Food Research. 2005;49(11):1044–1049.
    1. Slatter DA, Bolton CH, Bailey AJ. The importance of lipid-derived malondialdehyde in diabetes mellitus. Diabetologia. 2000;43(5):550–557.
    1. Bhutia Y, Ghosh A, Sherpa ML, Pal R, Mohanta PK. Serum malondialdehyde level: surrogate stress marker in the Sikkimese diabetics. Journal of Natural Science, Biology and Medicine. 2011;2(1):107–112.
    1. Mahreen R, Mohsin M, Nasreen Z, Siraj M, Ishaq M. Significantly increased levels of serum malonaldehyde in type 2 diabetics with myocardial infarction. International Journal of Diabetes in Developing Countries. 2010;30(1):49–51.
    1. Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of oxidative stress during diabetes mellitus. Journal of Biomarkers. 2013;2013:8 pages.378790
    1. Nakhjavani M, Esteghamati A, Nowroozi S, Asgarani F, Rashidi A, Khalilzadeh O. Type 2 diabetes mellitus duration: an independent predictor of serum malondialdehyde levels. Singapore Medical Journal. 2010;51(7):582–585.
    1. Wang CH, Chang RW, Ko YH, et al. Prevention of arterial stiffening by using low-dose atorvastatin in diabetes is associated with decreased malondialdehyde. PloS ONE. 2014;9(3)e90471
    1. Jaganjac M, Tirosh O, Cohen G, Sasson S, Zarkovic N. Reactive aldehydes—second messengers of free radicals in diabetes mellitus. Free Radical Research. 2013;47(supplement 1):39–48.
    1. Cohen G, Riahi Y, Shamni O, et al. Role of lipid peroxidation and PPAR-δ in amplifying glucose-stimulated insulin secretion. Diabetes. 2011;60(11):2830–2842.
    1. Pradeep AR, Agarwal E, Bajaj P, Rao NS. 4-Hydroxy-2-nonenal, an oxidative stress marker in crevicular fluid and serum in type 2 diabetes with chronic periodontitis. Contemporary Clinical Dentistry. 2013;4(3):281–285.
    1. Toyokuni S, Yamada S, Kashima M, et al. Serum 4-hydroxy-2-nonenal-modified albumin is elevated in patients with type 2 diabetes mellitus. Antioxidants and Redox Signaling. 2000;2(4):681–685.
    1. Cohen G, Riahi Y, Sunda V, et al. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes. Free Radical Biology and Medicine. 2013;65:978–987.
    1. Lupachyk S, Shevalye H, Maksimchyk Y, Drel VR, Obrosova IG. PARP inhibition alleviates diabetes-induced systemic oxidative stress and neural tissue 4-hydroxynonenal adduct accumulation: correlation with peripheral nerve function. Free Radical Biology and Medicine. 2011;50(10):1400–1409.
    1. Tuma DJ. Role of malondialdehyde-acetaldehyde adducts in liver injury. Free Radical Biology and Medicine. 2002;32(4):303–308.
    1. Sampey BP, Korourian S, Ronis MJ, Badger TM, Petersen DR. Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury. Alcoholism: Clinical and Experimental Research. 2003;27(6):1015–1022.
    1. Albano E. Role of adaptive immunity in alcoholic liver disease. International Journal of Hepatology. 2012;2012:7 pages.893026
    1. Thiele GM, Klassen LW, Tuma DJ. Formation and immunological properties of aldehyde-derived protein adducts following alcohol consumption. Methods in Molecular Biology. 2008;447:235–257.
    1. Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sciences. 2007;81(3):177–187.
    1. Niemelä O. Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radical Biology and Medicine. 2001;31(12):1533–1538.
    1. Mottaran E, Stewart SF, Rolla R, et al. Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease. Free Radical Biology and Medicine. 2002;32(1):38–45.
    1. Willis MS, Klassen LW, Tuma DJ, Sorrell MF, Thiele GM. Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation. Alcoholism: Clinical and Experimental Research. 2002;26(1):94–106.
    1. Dou X, Li S, Wang Z, et al. Inhibition of NF-κB activation by 4-hydroxynonenal contributes to liver injury in a mouse model of alcoholic liver disease. The American Journal of Pathology. 2012;181(5):1702–1710.
    1. Smathers RL, Galligan JJ, Stewart BJ, Petersen DR. Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease. Chemico-Biological Interactions. 2011;192(1-2):107–112.
    1. Poli G, Biasi F, Leonarduzzi G. 4-Hydroxynonenal-protein adducts: a reliable biomarker of lipid oxidation in liver diseases. Molecular Aspects of Medicine. 2008;29(1-2):67–71.
    1. Petersen DR, Doorn JA. Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radical Biology and Medicine. 2004;37(7):937–945.
    1. Galligan JJ, Smathers RL, Fritz KS, Epperson LE, Hunter LE, Petersen DR. Protein carbonylation in a murine model for early alcoholic liver disease. Chemical Research in Toxicology. 2012;25(5):1012–1021.
    1. Perluigi M, Coccia R, Butterfield DA. 4-Hydroxy-2-nonenal, a reactive product of lipid peroxidation, and neurodegenerative diseases: a toxic combination illuminated by redox proteomics studies. Antioxidants & Redox Signaling. 2012;17(11):1590–1609.
    1. Reed TT. Lipid peroxidation and neurodegenerative disease. Free Radical Biology and Medicine. 2011;51(7):1302–1319.
    1. Zarkovic K. 4-hydroxynonenal and neurodegenerative diseases. Molecular Aspects of Medicine. 2003;24(4-5):293–303.
    1. Selley ML. (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radical Biology and Medicine. 1998;25(2):169–174.
    1. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(7):2696–2701.
    1. Traverso N, Menini S, Maineri EP, et al. Malondialdehyde, a lipoperoxidation-derived aldehyde, can bring about secondary oxidative damage to proteins. Journals of Gerontology A: Biological Sciences and Medical Sciences. 2004;59(9):890–895.
    1. Tuma DJ, Kearley ML, Thiele GM, et al. Elucidation of reaction scheme describing malondialdehyde—acetaldehyde—protein adduct formation. Chemical Research in Toxicology. 2001;14(7):822–832.
    1. Wang G, Li H, Firoze Khan M. Differential oxidative modification of proteins in MRL+/+ and MRL/lpr mice: increased formation of lipid peroxidation-derived aldehyde-protein adducts may contribute to accelerated onset of autoimmune response. Free Radical Research. 2012;46(12):1472–1481.
    1. Duryee MJ, Klassen LW, Jones BL, Willis MS, Tuma DJ, Thiele GM. Increased immunogenicity to P815 cells modified with malondialdehyde and acetaldehyde. International Immunopharmacology. 2008;8(8):1112–1118.
    1. Wang G, Ansari GAS, Khan MF. Involvement of lipid peroxidation-derived aldehyde-protein adducts in autoimmunity mediated by trichloroethene. Journal of Toxicology and Environmental Health A: Current Issues. 2007;70(23):1977–1985.
    1. Wållberg M, Bergquist J, Achour A, Breij E, Harris RA. Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity. European Journal of Immunology. 2007;37(7):1986–1995.
    1. Weismann D, Binder CJ. The innate immune response to products of phospholipid peroxidation. Biochimica et Biophysica Acta: Biomembranes. 2012;1818(10):2465–2475.
    1. Slatter DA, Avery NC, Bailey AJ. Identification of a new cross-link and unique histidine adduct from bovine serum albumin incubated with malondialdehyde. Journal of Biological Chemistry. 2004;279(1):61–69.
    1. Cheng J, Wang F, Yu D-F, Wu P-F, Chen J-G. The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking/mitochondrial dysfunction/reactive oxygen species/MAPK pathway in neurons. European Journal of Pharmacology. 2011;650(1):184–194.
    1. Weismann D, Hartvigsen K, Lauer N, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature. 2011;478(7367):76–81.
    1. Veneskoski M, Turunen SP, Kummu O, et al. Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a. Free Radical Biology and Medicine. 2011;51(4):834–843.
    1. Kharbanda KK, Shubert KA, Wyatt TA, Sorrell MF, Tuma DJ. Effect of malondialdehyde-acetaldehyde-protein adducts on the protein kinase C-dependent secretion of urokinase-type plasminogen activator in hepatic stellate cells. Biochemical Pharmacology. 2002;63(3):553–562.
    1. Marnett LJ. Oxy radicals, lipid peroxidation and DNA damage. Toxicology. 2002;181-182:219–222.
    1. Marnett LJ. Lipid peroxidation-DNA damage by malondialdehyde. Mutation Research. 1999;424(1-2):83–95.
    1. Fink SP, Reddy GR, Marnett LJ. Mutagenicity in Escherichia coli of the major DNA adduct derived from the endogenous mutagen malondialdehyde. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(16):8652–8657.
    1. Vöhringer M-L, Becker TW, Krieger G, Jacobi H, Witte I. Synergistic DNA damaging effects of malondialdehyde/Cu(II) in PM2 DNA and in human fibroblasts. Toxicology Letters. 1998;94(3):159–166.
    1. Ji C, Rouzer CA, Marnett LJ, Pietenpol JA. Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde. Carcinogenesis. 1998;19(7):1275–1283.
    1. Willis MS, Klassen LW, Carlson DL, Brouse CF, Thiele GM. Malondialdehyde-acetaldehyde haptenated protein binds macrophage scavenger receptor(s) and induces lysosomal damage. International Immunopharmacology. 2004;4(7):885–899.
    1. Otteneder MB, Knutson CG, Daniels JS, et al. In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M1dG. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(17):6665–6669.
    1. Cline SD, Lodeiro MF, Marnett LJ, Cameron CE, Arnold JJ. Arrest of human mitochondrial RNA polymerase transcription by the biological aldehyde adduct of DNA, M1dG. Nucleic Acids Research. 2010;38(21):7546–7557.
    1. Sram RJ, Farmer P, Singh R, et al. Effect of vitamin levels on biomarkers of exposure and oxidative damage-the EXPAH study. Mutation Research: Genetic Toxicology and Environmental Mutagenesis. 2009;672(2):129–134.
    1. Spickett CM. The lipid peroxidation product 4-hydroxy-2-nonenal: advances in chemistry and analysis. Redox Biology. 2013;1(1):145–152.
    1. Usatyuk PV, Natarajan V. Hydroxyalkenals and oxidized phospholipids modulation of endothelial cytoskeleton, focal adhesion and adherens junction proteins in regulating endothelial barrier function. Microvascular Research. 2012;83(1):45–55.
    1. Sharma R, Sharma A, Chaudhary P, et al. Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane. Free Radical Biology and Medicine. 2012;52(11-12):2177–2185.
    1. Zimniak P. Relationship of electrophilic stress to aging. Free Radical Biology and Medicine. 2011;51(6):1087–1105.
    1. Fritz KS, Petersen DR. Exploring the biology of lipid peroxidation-derived protein carbonylation. Chemical Research in Toxicology. 2011;24(9):1411–1419.
    1. Butterfield DA, Reed T, Sultana R. Roles of 3-nitrotyrosine- and 4-hydroxynonenal-modified brain proteins in the progression and pathogenesis of Alzheimer’s disease. Free Radical Research. 2011;45(1):59–72.
    1. Balogh LM, Atkins WM. Interactions of glutathione transferases with 4-hydroxynonenal. Drug Metabolism Reviews. 2011;43(2):165–178.
    1. Klil-Drori AJ, Ariel A. 15-Lipoxygenases in cancer: a double-edged sword? Prostaglandins & Other Lipid Mediators. 2013;106:16–22.
    1. Brash AR, Boeglin WE, Chang MS. Discovery of a second 15S-lipoxygenase in humans. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(12):6148–6152.
    1. Ivanov I, Heydeck D, Hofheinz K, et al. Molecular enzymology of lipoxygenases. Archives of Biochemistry and Biophysics. 2010;503(2):161–174.
    1. Takamura H, Gardner HW. Oxygenation of (3Z)-alkenal to (2E)-4-hydroxy-2-alkenal in soybean seed (Glycine max L.) Biochimica et Biophysica Acta: Lipids and Lipid Metabolism. 1996;1303(2):83–91.
    1. Schneider C, Tallman KA, Porter NA, Brash AR. Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals. Journal of Biological Chemistry. 2001;276(24):20831–20838.
    1. Riahi Y, Cohen G, Shamni O, Sasson S. Signaling and cytotoxic functions of 4-hydroxyalkenals. American Journal of Physiology: Endocrinology and Metabolism. 2010;299(6):E879–E886.
    1. Mahipal SVK, Subhashini J, Reddy MC, et al. Effect of 15-lipoxygenase metabolites, 15-(S)-HPETE and 15-(S)-HETE on chronic myelogenous leukemia cell line K-562: reactive oxygen species (ROS) mediate caspase-dependent apoptosis. Biochemical Pharmacology. 2007;74(2):202–214.
    1. Kumar KA, Arunasree KM, Roy KR, et al. Effects of (15S)-hydroperoxyeicosatetraenoic acid and (15S)-hydroxyeicosatetraenoic acid on the acute-lymphoblastic-leukaemia cell line Jurkat: activation of the Fas-mediated death pathway. Biotechnology and Applied Biochemistry. 2009;52(2):121–133.
    1. Eckl PM. Genotoxicity of HNE. Molecular Aspects of Medicine. 2003;24(4-5):161–165.
    1. Siems W, Grune T. Intracellular metabolism of 4-hydroxynonenal. Molecular Aspects of Medicine. 2003;24(4-5):167–175.
    1. Alary J, Guéraud F, Cravedi J-P. Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways. Molecular Aspects of Medicine. 2003;24(4-5):177–187.
    1. McElhanon KE, Bose C, Sharma R, Wu L, Awasthi YC, Singh SP. Gsta4 null mouse embryonic fibroblasts exhibit enhanced sensitivity to oxidants: role of 4-hydroxynonenal in oxidant toxicity. Open Journal of Apoptosis. 2013;2(1)
    1. Black W, Chen Y, Matsumoto A, et al. Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal. Free Radical Biology and Medicine. 2012;52(9):1937–1944.
    1. Kong D, Kotraiah V. Modulation of aldehyde dehydrogenase activity affects (±)-4-hydroxy-2E-nonenal (HNE) toxicity and HNE-protein adduct levels in PC12 cells. Journal of Molecular Neuroscience. 2012;47(3):595–603.
    1. Huang Y, Li W, Kong ANT. Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal. Cell & Bioscience. 2012;2(1, article 40)
    1. Zhang Y, Sano M, Shinmura K, et al. 4-Hydroxy-2-nonenal protects against cardiac ischemia-reperfusion injury via the Nrf2-dependent pathway. Journal of Molecular and Cellular Cardiology. 2010;49(4):576–586.
    1. Siow RCM, Ishii T, Mann GE. Modulation of antioxidant gene expression by 4-hydroxynonenal: atheroprotective role of the Nrf2/ARE transcription pathway. Redox Report. 2007;12(1-2):11–15.
    1. Tanito M, Agbaga M-P, Anderson RE. Upregulation of thioredoxin system via Nrf2-antioxidant responsive element pathway in adaptive-retinal neuroprotection in vivo and in vitro. Free Radical Biology and Medicine. 2007;42(12):1838–1850.
    1. Ishii T, Itoh K, Ruiz E, et al. Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circulation Research. 2004;94(5):609–616.
    1. Miller DM, Singh IN, Wang JA, Hall ED. Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo. Free Radical Biology and Medicine. 2013;57:1–9.
    1. Gan L, Johnson JA. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochimica et Biophysica Acta: Molecular Basis of Disease. 2013
    1. Na HK, Surh YJ. Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1. Free Radical Biology and Medicine. 2014;67:353–365.
    1. Seo HA, Lee IK. The role of Nrf2: adipocyte differentiation, obesity, and insulin resistance. Oxidative Medicine and Cellular Longevity. 2013;2013:7 pages.184598
    1. Deramaudt TB, Dill C, Bonay M. Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases. Médecine et Maladies Infectieuses. 2013;43(3):100–107.
    1. Grochot-Przeczek A, Dulak J, Jozkowicz A. Haem oxygenase-1: non-canonical roles in physiology and pathology. Clinical Science. 2012;122(3):93–103.
    1. Lin MH, Yen JH, Weng CY, Wang L, Ha CL, Wu MJ. Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded protein response and heme oxygenase-1 expression in PC12 cells: roles of ROS and MAPK pathways. Toxicology. 2014;315:24–37.
    1. Ishikado A, Nishio Y, Morino K, et al. Low concentration of 4-hydroxy hexenal increases heme oxygenase-1 expression through activation of Nrf2 and antioxidative activity in vascular endothelial cells. Biochemical and Biophysical Research Communications. 2010;402(1):99–104.
    1. Ueda K, Ueyama T, Yoshida K-I, et al. Adaptive HNE-Nrf2-HO-1 pathway against oxidative stress is associated with acute gastric mucosal lesions. American Journal of Physiology: Gastrointestinal and Liver Physiology. 2008;295(3):G460–G469.
    1. Holmgren A, Lu J. Thioredoxin and thioredoxin reductase: current research with special reference to human disease. Biochemical and Biophysical Research Communications. 2010;396(1):120–124.
    1. Chen Z-H, Saito Y, Yoshida Y, Sekine A, Noguchi N, Niki E. 4-hydroxynonenal induces adaptive response and enhances PC12 cell tolerance primarily through induction of thioredoxin reductase 1 via activation of Nrf2. Journal of Biological Chemistry. 2005;280(51):41921–41927.
    1. Lu SC. Glutathione synthesis. Biochimica et Biophysica Acta. 2013;1830(5):3143–3153.
    1. Franklin CC, Backos DS, Mohar I, White CC, Forman HJ, Kavanagh TJ. Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Molecular Aspects of Medicine. 2009;30(1-2):86–98.
    1. Backos DS, Fritz KS, Roede JR, Petersen DR, Franklin CC. Posttranslational modification and regulation of glutamate-cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal. Free Radical Biology and Medicine. 2011;50(1):14–26.
    1. Zhang H, Shih A, Rinna A, Forman HJ. Resveratrol and 4-hydroxynonenal act in concert to increase glutamate cysteine ligase expression and glutathione in human bronchial epithelial cells. Archives of Biochemistry and Biophysics. 2009;481(1):110–115.
    1. Zhang H, Court N, Forman HJ. Submicromolar concentrations of 4-hydroxynonenal induce glutamate cysteine ligase expression in HBE1 cells. Redox Report. 2007;12(1-2):101–106.
    1. Iles KE, Liu R-M. Mechanisms of Glutamate Cysteine Ligase (GCL) induction by 4-hydroxynonenal. Free Radical Biology and Medicine. 2005;38(5):547–556.
    1. Forman HJ, Dickinson DA, Iles KE. HNE—signaling pathways leading to its elimination. Molecular Aspects of Medicine. 2003;24(4-5):189–194.
    1. Braithwaite EK, Mattie MD, Freedman JH. Activation of metallothionein transcription by 4-hydroxynonenal. Journal of Biochemical and Molecular Toxicology. 2010;24(5):330–334.
    1. Reichard JF, Petersen DR. Hepatic stellate cells lack AP-1 responsiveness to electrophiles and phorbol 12-myristate-13-acetate. Biochemical and Biophysical Research Communications. 2004;322(3):842–853.
    1. Kikuta K, Masamune A, Satoh M, Suzuki N, Shimosegawa T. 4-Hydroxy-2, 3-nonenal activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells. World Journal of Gastroenterology. 2004;10(16):2344–2351.
    1. Camandola S, Poli G, Mattson MP. The lipid peroxidation product 4-hydroxy-2,3-nonenal increases AP-1- binding activity through caspase activation in neurons. Journal of Neurochemistry. 2000;74(1):159–168.
    1. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nature Cell Biology. 2002;4(5):E131–E136.
    1. Shaulian E. AP-1—the Jun proteins: oncogenes or tumor suppressors in disguise? Cellular Signalling. 2010;22(6):894–899.
    1. Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Research. 2011;21(1):103–115.
    1. Siomek A. NF-κB signaling pathway and free radical impact. Acta Biochimica Polonica. 2012;59(3):323–331.
    1. Lim JH, Lee J-C, Lee YH, et al. Simvastatin prevents oxygen and glucose deprivation/reoxygenation-induced death of cortical neurons by reducing the production and toxicity of 4-hydroxy-2E-nonenal. Journal of Neurochemistry. 2006;97(1):140–150.
    1. Kaarniranta K, Ryhänen T, Karjalainen HM, et al. Geldanamycin increases 4-hydroxynonenal (HNE)-induced cell death in human retinal pigment epithelial cells. Neuroscience Letters. 2005;382(1-2):185–190.
    1. Luckey SW, Taylor M, Sampey BP, Scheinman RI, Petersen DR. 4-Hydroxynonenal decreases interleukin-6 expression and protein production in primary rat Kupffer cells by inhibiting nuclear factor-κB activation. Journal of Pharmacology and Experimental Therapeutics. 2002;302(1):296–303.
    1. Minekura H, Kumagai T, Kawamoto Y, Nara F, Uchida K. 4-Hydroxy-2-nonenal is a powerful endogenous inhibitor of endothelial response. Biochemical and Biophysical Research Communications. 2001;282(2):557–561.
    1. Ji C, Kozak KR, Marnett LJ. IκB kinase, a molecular target for inhibition by 4-hydroxy-2-nonenal. Journal of Biological Chemistry. 2001;276(21):18223–18228.
    1. Lee SJ, Kim CE, Seo KW, Kim CD. HNE-induced 5-LO expression is regulated by NF-κB/ERK and Sp1/p38 MAPK pathways via EGF receptor in murine macrophages. Cardiovascular Research. 2010;88(2):352–359.
    1. Lee SJ, Seo KW, Yun MR, et al. 4-hydroxynonenal enhances MMP-2 production in vascular smooth muscle cells via mitochondrial ROS-mediated activation of the Akt/NF-κB signaling pathways. Free Radical Biology and Medicine. 2008;45(10):1487–1492.
    1. Raza H, John A, Brown EM, Benedict S, Kambal A. Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicology and Applied Pharmacology. 2008;226(2):161–168.
    1. Malone PE, Hernandez MR. 4-Hydroxynonenal, a product of oxidative stress, leads to an antioxidant response in optic nerve head astrocytes. Experimental Eye Research. 2007;84(3):444–454.
    1. Vaillancourt F, Morquette B, Shi Q, et al. Differential regulation of cyclooxygenase-2 and inducible nitric oxide synthase by 4-hydroxynonenal in human osteoarthritic chondrocytes through ATF-2/CREB-1 transactivation and concomitant inhibition of NF-κB signaling cascade. Journal of Cellular Biochemistry. 2007;100(5):1217–1231.
    1. Amma H, Naruse K, Ishiguro N, Sokabe M. Involvement of reactive oxygen species in cyclic stretch-induced NF-κB activation in human fibroblast cells. British Journal of Pharmacology. 2005;145(3):364–373.
    1. Donath B, Fischer C, Page S, et al. Chlamydia pneumoniae activates IKK/IκB-mediated signaling, which is inhibited by 4-HNE and following primary exposure. Atherosclerosis. 2002;165(1):79–88.
    1. Kim T, Yang Q. Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system. World Journal of Cardiology. 2013;5(6):164–174.
    1. Ahmadian M, Suh JM, Hah N, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nature Medicine. 2013;19(5):557–566.
    1. Barrera G, Toaldo C, Pizzimenti S, et al. The role of PPAR ligands in controlling growth-related gene expression and their interaction with lipoperoxidation products. PPAR Research. 2008;2008:15 pages.524671
    1. Wang Z, Dou X, Gu D, et al. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARγ and accelerating ubiquitin-proteasome degradation. Molecular and Cellular Endocrinology. 2012;349(2):222–231.
    1. Pizzimenti S, Laurora S, Briatore F, Ferretti C, Dianzani MU, Barrera G. Synergistic effect of 4-hydroxynonenal and PPAR ligands in controlling human leukemic cell growth and differentiation. Free Radical Biology and Medicine. 2002;32(3):233–245.
    1. Cerbone A, Toaldo C, Laurora S, et al. 4-hydroxynonenal and PPARγ ligands affect proliferation, differentiation, and apoptosis in colon cancer cells. Free Radical Biology and Medicine. 2007;42(11):1661–1670.
    1. Almeida M, Ambrogini E, Han L, Manolagas SC, Jilka RL. Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-γ expression, and diminished pro-osteogenic Wnt signaling in the skeleton. Journal of Biological Chemistry. 2009;284(40):27438–27448.
    1. Coleman JD, Prabhu KS, Thompson JT, et al. The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) Free Radical Biology and Medicine. 2007;42(8):1155–1164.
    1. Zheng R, Po I, Mishin V, et al. The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard. Toxicology and Applied Pharmacology. 2013;272(2):345–355.
    1. Zheng R, Heck DE, Mishin V, et al. Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product. Toxicology and Applied Pharmacology. 2014;275(2):113–121.
    1. Uchida K, Kumagai T. 4-Hydroxy-2-nonenal as a COX-2 inducer. Molecular Aspects of Medicine. 2003;24(4-5):213–218.
    1. Parola M, Robino G, Marra F, et al. HNE interacts directly with JNK isoforms in human hepatic stellate cells. Journal of Clinical Investigation. 1998;102(11):1942–1950.
    1. Rinna A, Forman HJ. SHP-1 inhibition by 4-hydroxynonenal activates Jun N-terminal kinase and glutamate cysteine ligase. American Journal of Respiratory Cell and Molecular Biology. 2008;39(1):97–104.
    1. Liu R-M, Borok Z, Forman HJ. 4-Hydroxy-2-nonenal increases γ-glutamylcysteine synthetase gene expression in alveolar epithelial cells. American Journal of Respiratory Cell and Molecular Biology. 2001;24(4):499–505.
    1. Dickinson DA, Iles KE, Watanabe N, et al. 4-Hydroxynonenal induces glutamate cysteine ligase through JNK in HBE1 cells. Free Radical Biology and Medicine. 2002;33(7):974–987.
    1. Marantos C, Mukaro V, Ferrante J, Hii C, Ferrante A. Inhibition of the lipopolysaccharide-induced stimulation of the members of the MAPK family in human monocytes/macrophages by 4-hydroxynonenal, a product of oxidized omega-6 fatty acids. American Journal of Pathology. 2008;173(4):1057–1066.
    1. Shi Q, Vaillancourt F, Côté V, et al. Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid peroxidation end product 4-hydroxynonenal. Arthritis Research and Therapy. 2006;8(6, article R159)
    1. Usatyuk PV, Parinandi NL, Natarajan V. Redox regulation of 4-hydroxy-2-nonenal-mediated endothelial barrier dysfunction by focal adhesion, adherens, and tight junction proteins. Journal of Biological Chemistry. 2006;281(46):35554–35566.
    1. Shibata N, Kato Y, Inose Y, et al. 4-hydroxy-2-nonenal upregulates and phosphorylates cytosolic phospholipase A2 in cultured Ra2 microglial cells via MAPK pathways. Neuropathology. 2011;31(2):122–128.
    1. Verslegers M, Lemmens K, Van Hove I, Moons L. Matrix metalloproteinase-2 and -9 as promising benefactors in development, plasticity and repair of the nervous system. Progress in Neurobiology. 2013;105:60–78.
    1. Lee SJ, Kim CE, Yun MR, et al. 4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK. Toxicology and Applied Pharmacology. 2010;242(2):191–198.
    1. Seo KW, Lee SJ, Kim CE, et al. Participation of 5-lipoxygenase-derived LTB4 in 4-hydroxynonenal-enhanced MMP-2 production in vascular smooth muscle cells. Atherosclerosis. 2010;208(1):56–61.
    1. Morquette B, Shi Q, Lavigne P, Ranger P, Fernandes JC, Benderdour M. Production of lipid peroxidation products in osteoarthritic tissues: new evidence linking 4-hydroxynonenal to cartilage degradation. Arthritis and Rheumatism. 2006;54(1):271–281.
    1. Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. Cell Signaling. 2011;23(10):1515–1527.
    1. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annual Review of Pathology. 2009;4:127–150.
    1. Shearn CT, Fritz KS, Reigan P, Petersen DR. Modification of Akt2 by 4-hydroxynonenal inhibits insulin-dependent Akt signaling in HepG2 cells. Biochemistry. 2011;50(19):3984–3996.
    1. Shearn CT, Smathers RL, Backos DS, Reigan P, Orlicky DJ, Petersen DR. Increased carbonylation of the lipid phosphatase PTEN contributes to Akt2 activation in a murine model of early alcohol-induced steatosis. Free Radical Biology and Medicine. 2013;65:680–692.
    1. Shearn CT, Reigan P, Petersen DR. Inhibition of Hydrogen peroxide signaling by 4-hydroxynonenal due to differential regulation of Akt1 and Akt2 contributes to decreases in cell survival and proliferation in hepatocellular carcinoma cells. Free Radical Biology and Medicine. 2012;53(1):1–11.
    1. Vatsyayan R, Chaudhary P, Sharma A, et al. Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells. Experimental Eye Research. 2011;92(2):147–154.
    1. Turban S, Hajduch E. Protein kinase C isoforms: mediators of reactive lipid metabolites in the development of insulin resistance. FEBS Letters. 2011;585(2):269–274.
    1. Maggiora M, Rossi MA. The exocytosis induced in HL-60 cells by 4-hydroxynonenal, a lipid peroxidation product, is not prevented by reduced glutathione. Cell Biochemistry and Function. 2006;24(1):1–6.
    1. Maggiora M, Rossi MA. Experimental researches on the role of phosphoinositide-specific phospholipase C in 4-hydroxynonenal induced exocytosis. Cell Biochemistry and Function. 2003;21(2):155–160.
    1. Rossi MA, Di Mauro C, Dianzani MU. Experimental studies on the mechanism of phospholipase C activation by the lipid peroxidation products 4-hydroxynonenal and 2-nonenal. International Journal of Tissue Reactions. 2001;23(2):45–50.
    1. Rossi MA, Di Mauro C, Esterbauer H, Fidale F, Dianzani MU. Activation of phosphoinositide-specific phospholipase C of rat neutrophils by the chemotactic aldehydes 4-hydroxy-2,3-trans-nonenal and 4-hydroxy-2,3-trans-octenal. Cell Biochemistry and Function. 1994;12(4):275–280.
    1. de Oliveira-Junior EB, Bustamante J, Newburger PE, Condino-Neto A. The human NADPH oxidase: primary and secondary defects impairing the respiratory burst function and the microbicidal ability of phagocytes. Scandinavian Journal of Immunology. 2011;73(5):420–427.
    1. Harry RS, Hiatt LA, Kimmel DW, et al. Metabolic impact of 4-hydroxynonenal on macrophage-like RAW 264.7 function and activation. Chemical Research in Toxicology. 2012;25(8):1643–1651.
    1. Chiarpotto E, Domenicotti C, Paola D, et al. Regulation of rat hepatocyte protein kinase C β isoenzymes by the lipid peroxidation product 4-hydroxy-2,3-nonenal: a signaling pathway to modulate vesicular transport of glycoproteins. Hepatology. 1999;29(5):1565–1572.
    1. Paola D, Domenicotti C, Nitti M, et al. Oxidative stress induces increase in intracellular amyloid β-protein production and selective activation of βI and βII PKCs in NT2 cells. Biochemical and Biophysical Research Communications. 2000;268(2):642–646.
    1. Marinari UM, Nitti M, Pronzato MA, Domenicotti C. Role of PKC-dependent pathways in HNE-induced cell protein transport and secretion. Molecular Aspects of Medicine. 2003;24(4-5):205–211.
    1. Nitti M, Domenicotti C, D’Abramo C, et al. Activation of PKC-β isoforms mediates HNE-induced MCP-1 release by macrophages. Biochemical and Biophysical Research Communications. 2002;294(3):547–552.
    1. Ramana KV, Fadl AA, Tammali R, Reddy ABM, Chopra AK, Srivastava SK. Aldose reductase mediates the lipopolysaccharide-induced release of inflammatory mediators in RAW264.7 murine macrophages. Journal of Biological Chemistry. 2006;281(44):33019–33029.
    1. Dodson M, Darley-Usmar V, Zhang J. Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radical Biology and Medicine. 2013;63:207–221.
    1. Hill BG, Haberzettl P, Ahmed Y, Srivastava S, Bhatnagar A. Unsaturated lipid peroxidation-derived aldehydes activate autophagy in vascular smooth-muscle cells. Biochemical Journal. 2008;410(3):525–534.
    1. Haberzettl P, Hill BG. Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response. Redox Biology. 2013;1(1):56–64.
    1. Dodson M, Liang Q, Johnson MS, et al. Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells. Autophagy. 2013;9(12):1996–2008.
    1. Krohne TU, Stratmann NK, Kopitz J, Holz FG. Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells. Experimental Eye Research. 2010;90(3):465–471.
    1. Fyhrquist F, Saijonmaa O, Strandberg T. The roles of senescence and telomere shortening in cardiovascular disease. Nature Reviews Cardiology. 2013;10(5):274–283.
    1. Olive PL. Endogenous DNA breaks: gammaH2AX and the role of telomeres. Aging. 2009;1(2):154–156.
    1. Günes C, Rudolph KL. The role of telomeres in stem cells and cancer. Cell. 2013;152(3):390–393.
    1. Argüelles S, Machado A, Ayala A. Adduct formation of 4-hydroxynonenal and malondialdehyde with elongation factor-2 in vitro and in vivo. Free Radical Biology and Medicine. 2009;47(3):324–330.
    1. Wang C, Maddick M, Miwa S, et al. Adult-onset, short-term dietary restriction reduces cell senescence in mice. Aging. 2010;2(9):555–566.
    1. Nelson G, Wordsworth J, Wang C, et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell. 2012;11(2):345–349.
    1. Voghel G, Thorin-Trescases N, Farhat N, et al. Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients. Mechanisms of Ageing and Development. 2008;129(5):261–270.
    1. Pizzimenti S, Briatore F, Laurora S, et al. 4-Hydroxynonenal inhibits telomerase activity and hTERT expression in human leukemic cell lines. Free Radical Biology and Medicine. 2006;40(9):1578–1591.
    1. Pizzimenti S, Menegatti E, Berardi D, et al. 4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity. Journal of Nutritional Biochemistry. 2010;21(9):818–826.
    1. Rufini A, Tucci P, Celardo I, Melino G. Senescence and aging: the critical roles of p53. Oncogene. 2013;32(43):5129–5143.
    1. Qian Y, Chen X. Senescence regulation by the p53 protein family. Methods in Molecular Biology. 2013;965:37–61.
    1. Sahin E, DePinho RA. Axis of ageing: telomeres, p53 and mitochondria. Nature Reviews Molecular Cell Biology. 2012;13(6):397–404.
    1. Liu D, Xu Y. P53, oxidative stress, and aging. Antioxidants and Redox Signaling. 2011;15(6):1669–1678.
    1. Hafsi H, Hainaut P. Redox control and interplay between p53 isoforms: roles in the regulation of basal p53 levels, cell fate, and senescence. Antioxidants and Redox Signaling. 2011;15(6):1655–1667.
    1. Vigneron A, Vousden KH. p53, ROS and senescence in the control of aging. Aging. 2010;2(8):471–474.
    1. Verbon EH, Post JA, Boonstra J. The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene. 2012;511(1):1–6.
    1. Chiu J, Dawes IW. Redox control of cell proliferation. Trends in Cell Biology. 2012;22(11):592–601.
    1. Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140(15):3079–3093.
    1. Barrera G, Pizzimenti S, Laurora S, Moroni E, Giglioni B, Dianzani MU. 4-hydroxynonenal affects pRb/E2F pathway in HL-60 human leukemic cells. Biochemical and Biophysical Research Communications. 2002;295(2):267–275.
    1. Pizzimenti S, Barrera G, Dianzani MU, Brüsselbach S. Inhibition of D1, D2, and A cyclin expression in HL-60 cells by the lipid peroxydation product 4-hydroxynonenal. Free Radical Biology and Medicine. 1999;26(11-12):1578–1586.
    1. Skorokhod OA, Caione L, Marrocco T, et al. Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal. Blood. 2010;116(20):4328–4337.
    1. Albright CD, Klem E, Shah AA, Gallagher P. Breast cancer cell-targeted oxidative stress: enhancement of cancer cell uptake of conjugated linoleic acid, activation of p53, and inhibition of proliferation. Experimental and Molecular Pathology. 2005;79(2):118–125.
    1. Sunjic SB, Cipak A, Rabuzin F, Wildburger R, Zarkovic N. The influence of 4-hydroxy-2-nonenal on proliferation, differentiation and apoptosis of human osteosarcoma cells. BioFactors. 2005;24(1–4):141–148.
    1. Muzio G, Trombetta A, Martinasso G, Canuto RA, Maggiora M. Antisense oligonucleotides against aldehyde dehydrogenase 3 inhibit hepatoma cell proliferation by affecting MAP kinases. Chemico-Biological Interactions. 2003;143-144:37–43.
    1. Canuto RA, Muzio G, Ferro M, et al. Inhibition of class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines. Free Radical Biology and Medicine. 1999;26(3-4):333–340.
    1. Pizzimenti S, Barrera G, Calzavara E, et al. Down-regulation of Notch1 expression is involved in HL-60 cell growth inhibition induced by 4-hydroxynonenal, a product of lipid peroxidation. Medicinal Chemistry. 2008;4(6):551–557.
    1. Laurora S, Tamagno E, Briatore F, et al. 4-Hydroxynonenal modulation of p53 family gene expression in the SK-N-BE neuroblastoma cell line. Free Radical Biology and Medicine. 2005;38(2):215–225.
    1. Barrera G, Martinotti S, Fazio V, et al. Effect of 4-hydroxynonenal on c-myc expression. Toxicologic Pathology. 1987;15(2):238–240.
    1. Barrera G, Muraca R, Pizzimenti S, et al. Inhibition of c-myc expression induced by 4-hydroxynonenal, a product of lipid peroxidation, in the HL-60 human leukemic cell line. Biochemical and Biophysical Research Communications. 1994;203(1):553–561.
    1. Rinaldi M, Barrera G, Spinsanti P, et al. Growth inhibition and differentiation induction in murine erythroleukemia cells by 4-hydroxynonenal. Free Radical Research. 2001;34(6):629–637.
    1. Barrera G, Pizzimenti S, Dianzani MU. 4-Hydroxynonenal and regulation of cell cycle: effects on the pRb/E2F pathway. Free Radical Biology and Medicine. 2004;37(5):597–606.
    1. Barrera G, Pizzimenti S, Muraca R, et al. Effect of 4-hydroxynonenal on cell cycle progression and expression of differentiation-associated antigens in HL-60 cells. Free Radical Biology and Medicine. 1996;20(3):455–462.
    1. Chaudhary P, Sharma R, Sahu M, Vishwanatha JK, Awasthi S, Awasthi YC. 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway. Journal of Biological Chemistry. 2013;288(28):20532–20546.
    1. Wang X, Yang Y, Moore DR, Nimmo SL, Lightfoot SA, Huycke MM. 4-hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by enterococcus faecalis-infected macrophages. Gastroenterology. 2012;142(3):543–551.
    1. Pettazzoni P, Pizzimenti S, Toaldo C, et al. Induction of cell cycle arrest and DNA damage by the HDAC inhibitor panobinostat (LBH589) and the lipid peroxidation end product 4-hydroxynonenal in prostate cancer cells. Free Radical Biology and Medicine. 2011;50(2):313–322.
    1. Peng ZF, Koh CHV, Li QT, et al. Deciphering the mechanism of HNE-induced apoptosis in cultured murine cortical neurons: transcriptional responses and cellular pathways. Neuropharmacology. 2007;53(5):687–698.
    1. Lee T-J, Lee J-T, Moon S-K, Kim C-H, Park J-W, Kwon TK. Age-related differential growth rate and response to 4-hydroxynonenal in mouse aortic smooth muscle cells. International Journal of Molecular Medicine. 2006;17(1):29–35.
    1. Kakishita H, Hattori Y. Vascular smooth muscle cell activation and growth by 4-hydroxynonenal. Life Sciences. 2001;69(6):689–697.
    1. Tammali R, Saxena A, Srivastava SK, Ramana KV. Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle. Endocrinology. 2010;151(5):2140–2150.
    1. Huang C-D, Chen H-H, Wang C-H, et al. Human neutrophil-derived elastase induces airway smooth muscle cell proliferation. Life Sciences. 2004;74(20):2479–2492.
    1. Pizzimenti S, Toaldo C, Pettazzoni P, Dianzani MU, Barrera G. The “two-faced” effects of reactive oxygen species and the lipid peroxidation product 4-hydroxynonenal in the hallmarks of cancer. Cancers. 2010;2(2):338–363.
    1. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews Drug Discovery. 2009;8(7):579–591.
    1. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resistance Updates. 2004;7(2):97–110.
    1. Hileman EO, Liu J, Albitar M, Keating MJ, Huang P. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemotherapy and Pharmacology. 2004;53(3):209–219.
    1. Chaudhary P, Sharma R, Sharma A, et al. Mechanisms of 4-hydroxy-2-nonenal induced pro- and anti-apoptotic signaling. Biochemistry. 2010;49(29):6263–6275.
    1. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104(4):487–501.
    1. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic Pathology. 2007;35(4):495–516.
    1. Franklin JL. Redox regulation of the intrinsic pathway in neuronal apoptosis. Antioxidants and Redox Signaling. 2011;14(8):1437–1448.
    1. Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis—the p53 network. Journal of Cell Science. 2003;116(20):4077–4085.
    1. Abarikwu SO, Pant AB, Farombi EO. 4-hydroxynonenal induces mitochondrial-mediated apoptosis and oxidative stress in SH-SY5Y human neuronal cells. Basic and Clinical Pharmacology and Toxicology. 2012;110(5):441–448.
    1. Sharma A, Sharma R, Chaudhary P, et al. 4-hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells. Archives of Biochemistry and Biophysics. 2008;480(2):85–94.
    1. Sharma R, Sharma A, Dwivedi S, Zimniak P, Awasthi S, Awasthi YC. 4-hydroxynonenal self-limits Fas-mediated DISC-independent apoptosis by promoting export of Daxx from the nucleus to the cytosol and its binding to Fas. Biochemistry. 2008;47(1):143–156.
    1. Vaillancourt F, Fahmi H, Shi Q, et al. 4-hydroxynonenal induces apoptosis in human osteoarthritic chondrocytes: the protective role of glutathione-S-transferase. Arthritis Research and Therapy. 2008;10(5, article R107)
    1. Awasthi YC, Sharma R, Sharma A, et al. Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death. Free Radical Biology and Medicine. 2008;45(2):111–118.
    1. Doorn JA, Petersen DR. Covalent modification of amino acid nucleophiles by the lipid peroxidation products 4-hydroxy-2-nonenal and 4-oxo-2-nonenal. Chemical Research in Toxicology. 2002;15(11):1445–1450.
    1. Sayre LM, Lin D, Yuan Q, Zhu X, Tang X. Protein adducts generated from products of lipid oxidation: focus on HNE and ONE. Drug Metabolism Reviews. 2006;38(4):651–675.
    1. Monroy CA, Doorn JA, Roman DL. Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-Hydroxy-2-nonenal. Chemical Research in Toxicology . 2013;26(12):1832–1839.
    1. Poli G, Schaur RJ, Siems WG, Leonarduzzi G. 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Medicinal Research Reviews. 2008;28(4):569–631.
    1. Choudhury S, Pan J, Amin S, Chung F-L, Roy R. Repair kinetics of trans-4-Hydroxynonenal-induced cyclic 1,N2-propanodeoxyguanine DNA adducts by human cell nuclear extracts. Biochemistry. 2004;43(23):7514–7521.
    1. Choudhury S, Dyba M, Pan J, Roy R, Chung FL. Repair kinetics of acrolein- and (E)-4-hydroxy-2-nonenal-derived DNA adducts in human colon cell extracts. Mutation Research. 2013;751-752:15–23.
    1. Gros L, Ishchenko AA, Saparbaev M. Enzymology of repair of etheno-adducts. Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis. 2003;531(1-2):219–229.
    1. Nair J, Srivatanakul P, Haas C, et al. High urinary excretion of lipid peroxidation-derived DNA damage in patients with cancer-prone liver diseases. Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis. 2010;683(1-2):23–28.
    1. Nair J, Gansauge F, Beger H, Dolara P, Winde G, Bartsch H. Increased etheno-DNA adducts in affected tissues of patients suffering from Crohn’s disease, ulcerative colitis, and chronic pancreatitis. Antioxidants and Redox Signaling. 2006;8(5-6):1003–1010.
    1. Richard S, Lewis J. Hazardous Chemicals Desk Reference. John Wiley & Sons; 2008.
    1. Ayala A, Parrado J, Bougria M, Machado A. Effect of oxidative stress, produced by cumene hydroperoxide, on the various steps of protein synthesis. Modifications of elongation factor-2. Journal of Biological Chemistry. 1996;271(38):23105–23110.
    1. Parrado J, Bougria M, Ayala A, Castaño A, Machado A. Effects of aging on the various steps of protein synthesis: fragmentation of elongation factor 2. Free Radical Biology and Medicine. 1999;26(3-4):362–370.
    1. Parrado J, Bougria M, Ayala A, MacHado A. Induced mono-(ADP)-ribosylation of rat liver cytosolic proteins by lipid peroxidant agents. Free Radical Biology and Medicine. 1999;26(9-10):1079–1084.
    1. Parrado J, Absi EH, Machado A, Ayala A. ‘In vitro’ effect of cumene hydroperoxide on hepatic elongation factor-2 and its protection by melatonin. Biochimica et Biophysica Acta: General Subjects. 2003;1624(1–3):139–144.
    1. Argüelles S, Machado A, Ayala A. ‘In vitro’ effect of lipid peroxidation metabolites on elongation factor-2. Biochimica et Biophysica Acta: General Subjects. 2006;1760(3):445–452.
    1. Arguelles S, Cano M, Machado A, Ayala A. Effect of aging and oxidative stress on elongation factor-2 in hypothalamus and hypophysis. Mechanisms of Ageing and Development. 2011;132(1-2):55–64.
    1. Argüelles S, Muñoz MF, Cano M, Machado A, Ayala A. In vitro and in vivo protection by melatonin against the decline of elongation factor-2 caused by lipid peroxidation: preservation of protein synthesis. Journal of Pineal Research. 2012;53(1):1–10.
    1. Argüelles S, Machado A, Ayala A. ’In vitro’ protective effect of a hydrophilic vitamin E analogue on the decrease in levels of elongation factor 2 in conditions of oxidative stress. Gerontology. 2007;53(5):282–288.
    1. Arguelles S, Cano M, Machado A, Ayala A. Comparative study of the In Vitro protective effects of several antioxidants on elongation factor 2 under oxidative stress conditions. Bioscience, Biotechnology and Biochemistry. 2010;74(7):1373–1379.
    1. Argüelles S, Camandola S, Hutchison ER, Cutler RG, Ayala A, Mattson MP. Molecular control of the amount, subcellular location, and activity state of translation elongation factor 2 in neurons experiencing stress. Free Radical Biology and Medicine. 2013;61:61–71.
    1. Argüelles S, Camandola S, Cutler RG, Ayala A, Mattson MP. Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions. Free Radical Biology and Medicine. 2013;67:131–138.
    1. Aboua YG, Brooks N, Mahfouz RZ, Agarwal A, du Plessis SS. A red palm oil diet can reduce the effects of oxidative stress on rat spermatozoa. Andrologia. 2012;44(supplement 1):32–40.
    1. Kumar TR, Muralidhara M. Induction of oxidative stress by organic hydroperoxides in testis and epididymal sperm of rats in vivo. Journal of Andrology. 2007;28(1):77–85.
    1. Chan TS, Shangari N, Wilson JX, Chan H, Butterworth RF, O’Brien PJ. The biosynthesis of ascorbate protects isolated rat hepatocytes from cumene hydroperoxide-mediated oxidative stress. Free Radical Biology and Medicine. 2005;38(7):867–873.
    1. Shvedova AA, Kisin ER, Murray AR, et al. Antioxidant balance and free radical generation in vitamin E-deficient mice after dermal exposure to cumene hydroperoxide. Chemical Research in Toxicology. 2002;15(11):1451–1459.
    1. Alam A, Iqbal M, Saleem M, Ahmed S-U, Sultana S. Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice. Pharmacology and Toxicology. 2000;86(5):209–214.
    1. Jamal M, Masood A, Belcastro R, et al. Lipid hydroperoxide formation regulates postnatal rat lung cell apoptosis and alveologenesis. Free Radical Biology and Medicine. 2013;55:83–92.
    1. Hong CO, Rhee CH, Won NH, Choi HD, Lee KW. Protective effect of 70% ethanolic extract of Lindera obtusiloba Blume on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in rats. Food and Chemical Toxicology. 2013;53:214–220.
    1. Oh JM, Jung YS, Jeon BS, et al. Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide. Food and Chemical Toxicology. 2012;50(5):1215–1221.
    1. Kim M-K, Lee H-S, Kim E-J, et al. Protective effect of aqueous extract of Perilla frutescens on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in rats. Food and Chemical Toxicology. 2007;45(9):1738–1744.
    1. Kaur P, Kaur G, Bansal MP. Tertiary-butyl hydroperoxide induced oxidative stress and male reproductive activity in mice: role of transcription factor NF-κB and testicular antioxidant enzymes. Reproductive Toxicology. 2006;22(3):479–484.
    1. Liu CL, Wang JM, Chu CY, Cheng MT, Tseng TH. In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity. Food and Chemical Toxicology. 2002;40(5):635–641.
    1. Hix S, Kadiiska MB, Mason RP, Augusto O. In vivo metabolism of tert-Butyl hydroperoxide to methyl radicals. EPR spin-trapping and DNA methylation studies. Chemical Research in Toxicology. 2000;13(10):1056–1064.
    1. Ma JQ, Ding J, Zhang L, Liu CM. Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway. Food and Chemical Toxicology. 2013;64:41–48.
    1. Yeh YH, Hsieh YL, Lee YT. Effects of yam peel extract against carbon tetrachloride-induced hepatotoxicity in rats. Journal of Agricultural and Food Chemistry. 2013;61(30):7387–7396.
    1. Knockaert L, Berson A, Ribault C, et al. Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver. Laboratory Investigation. 2012;92(3):396–410.
    1. Choi J-H, Kim D-W, Yun N, et al. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. Journal of Natural Products. 2011;74(5):1055–1060.
    1. Kim H-Y, Kim J-K, Choi J-H, et al. Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice. Journal of Pharmacological Sciences. 2010;112(1):105–112.
    1. Wang H, Wei W, Wang N-P, et al. Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress. Life Sciences. 2005;77(15):1902–1915.
    1. Lugo-Huitrón R, Ugalde Muñiz P, Pineda B, Pedraza-Chaverrí J, Ríos C, Pérez-de la Cruz V. Quinolinic acid: an endogenous neurotoxin with multiple targets. Oxidative Medicine and Cellular Longevity. 2013;2013:14 pages.104024
    1. Maldonado PD, Pérez-De La Cruz V, Torres-Ramos M, et al. Selenium-induced antioxidant protection recruits modulation of thioredoxin reductase during excitotoxic/pro-oxidant events in the rat striatum. Neurochemistry International. 2012;61(2):195–206.
    1. Sreekala S, Indira M. Impact of co administration of selenium and quinolinic acid in the rat’s brain. Brain Research. 2009;1281:101–107.
    1. Ryu JK, Choi HB, McLarnon JG. Peripheral benzodiazepine receptor ligand PK11195 reduces microglial activation and neuronal death in quinolinic acid-injected rat striatum. Neurobiology of Disease. 2005;20(2):550–561.
    1. Rossato JI, Zeni G, Mello CF, Rubin MA, Rocha JBT. Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat. Neuroscience Letters. 2002;318(3):137–140.
    1. Santamaría A, Jiménez-Capdeville ME, Camacho A, Rodríguez-Martínez E, Flores A, Galván-Arzate S. In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. NeuroReport. 2001;12(12):2693–2696.
    1. Rodríguez-Martínez E, Camacho A, Maldonado PD, et al. Effect of quinolinic acid on endogenous antioxidants in rat corpus striatum. Brain Research. 2000;858(2):436–439.
    1. Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011;283(2-3):65–87.
    1. Boveris A, Musacco-Sebio R, Ferrarotti N, et al. The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage in rat liver. Journal of Inorganic Biochemistry. 2012;116:63–69.
    1. Özcelik D, Uzun H, Naziroglu M. N-acetylcysteine attenuates copper overload-induced oxidative injury in brain of rat. Biological Trace Element Research. 2012;147(1–3):292–298.
    1. Alexandrova A, Petrov L, Georgieva A, et al. Effect of copper intoxication on rat liver proteasome activity: relationship with oxidative stress. Journal of Biochemical and Molecular Toxicology. 2008;22(5):354–362.
    1. Scharf B, Trombetta LD. The effects of the wood preservative copper dimethyldithiocarbamate in the hippocampus of maternal and newborn Long-Evans rats. Toxicology Letters. 2007;174(1-3):117–124.
    1. Parveen K, Khan MR, Siddiqui WA. Pycnogenol prevents potassium dichromate (K2Cr2O7)-induced oxidative damage and nephrotoxicity in rats. Chemico-Biological Interactions. 2009;181(3):343–350.
    1. Kotyzova D, Hodková A, Bludovská M, Eybl V. Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat. Toxicology and Industrial Health. In press.
    1. Karaca S, Eraslan G. The effects of flaxseed oil on cadmium-induced oxidative stress in rats. Biological Trace Element Research. 2013;155(3):423–430.
    1. Chen Q, Zhang R, Li W, et al. The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice. Environmental Toxicology and Pharmacology. 2013;36(3):759–768.
    1. Leelavinothan P, Kalist S. Beneficial effect of hesperetin on cadmium induced oxidative stress in rats: an in vivo and in vitro study. European Review for Medical and Pharmacological Sciences. 2011;15(9):992–1002.
    1. Ognjanović BI, Marković SD, Ethordević NZ, Trbojević IS, Stajn AS, Saicić ZS. Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q(10) and vitamin E. Reproductive Toxicology. 2010;29(2):191–197.
    1. Amudha K, Pari L. Beneficial role of naringin, a flavanoid on nickel induced nephrotoxicity in rats. Chemico-Biological Interactions. 2011;193(1):57–64.
    1. Pari L, Amudha K. Hepatoprotective role of naringin on nickel-induced toxicity in male Wistar rats. European Journal of Pharmacology. 2011;650(1):364–370.
    1. Scibior A, Gołębiowska D, Niedźwiecka I. Magnesium can protect against vanadium-induced lipid peroxidation in the hepatic tissue. Oxidative Medicine and Cellular Longevity. 2013;2013:11 pages.802734
    1. Ścibior A, Zaporowska H, Niedźwiecka I. Lipid peroxidation in the kidney of rats treated with V and/or Mg in drinking water. Journal of Applied Toxicology. 2010;30(5):487–496.
    1. Ścibior A, Zaporowska H, Ostrowski J, Banach A. Combined effect of vanadium(V) and chromium(III) on lipid peroxidation in liver and kidney of rats. Chemico-Biological Interactions. 2006;159(3):213–222.
    1. Martins EN, Pessano NTC, Leal L, et al. Protective effect of Melissa officinalis aqueous extract against Mn-induced oxidative stress in chronically exposed mice. Brain Research Bulletin. 2012;87(1):74–79.
    1. Chtourou Y, Fetoui H, Sefi M, et al. Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats. BioMetals. 2010;23(6):985–996.
    1. Chen MT, Cheng GW, Lin CC, Chen BH, Huang YL. Effects of acute manganese chloride exposure on lipid peroxidation and alteration of trace metals in rat brain. Biological Trace Element Research. 2006;110(2):163–178.
    1. Salama SA, Omar HA, Maghrabi IA, Alsaeed MS, El-Tarras AE. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats. Toxicology and Applied Pharmacology. 2014;274(1):1–6.
    1. Kim J, Paik HD, Yoon YC, Park E. Whey protein inhibits iron overload-induced oxidative stress in rats. Journal of Nutritional Science and Vitaminology. 2013;59(3):198–205.
    1. Arruda LF, Arruda SF, Campos NA, de Valencia FF, de Siqueira EM. Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats. PloS ONE. 2013;8(4)e61058
    1. Yu HC, Feng SF, Chao PL, Lin AMY. Anti-inflammatory effects of pioglitazone on iron-induced oxidative injury in the nigrostriatal dopaminergic system. Neuropathology and Applied Neurobiology. 2010;36(7):612–622.
    1. Oktar S, Yönden Z, Aydin M, Ilhan S, Alçin E, Oztürk OH. Protective effects of caffeic acid phenethyl ester on iron-induced liver damage in rats. Journal of Physiology and Biochemistry. 2009;65(4):339–344.
    1. Kokoszko A, Dabrowski J, Lewiński A, Karbownik-Lewińska M. Protective effects of GH and IGF-I against iron-induced lipid peroxidation in vivo. Experimental and Toxicologic Pathology. 2008;60(6):453–458.
    1. Maharaj DS, Maharaj H, Daya S, Glass BD. Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity. Journal of Neurochemistry. 2006;96(1):78–81.
    1. Morales NP, Yamaguchi Y, Murakami K, Kosem N, Utsumi H. Hepatic reduction of carbamoyl-PROXYL in ferric nitrilotriacetate induced iron overloaded mice: an in vivo ESR study. Biological and Pharmaceutical Bulletin. 2012;35(7):1035–1040.
    1. Völkel W, Alvarez-Sánchez R, Weick I, Mally A, Dekant W, Pähler A. Glutathione conjugates of 4-hydroxy-2(E)-nonenal as biomarkers of hepatic oxidative stress-induced lipid peroxidation in rats. Free Radical Biology and Medicine. 2005;38(11):1526–1536.
    1. Eybl V, Kotyzová D, Černá P, Koutenský J. Effect of melatonin, curcumin, quercetin, and resveratrol on acute ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative damage in rat. Human and Experimental Toxicology. 2008;27(4):347–353.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj