The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study

Adolfo Daniel Rodríguez-Carrizalez, José Alberto Castellanos-González, Esaú César Martínez-Romero, Guillermo Miller-Arrevillaga, Fermín Paul Pacheco-Moisés, Luis Miguel Román-Pintos, Alejandra Guillermina Miranda-Díaz, Adolfo Daniel Rodríguez-Carrizalez, José Alberto Castellanos-González, Esaú César Martínez-Romero, Guillermo Miller-Arrevillaga, Fermín Paul Pacheco-Moisés, Luis Miguel Román-Pintos, Alejandra Guillermina Miranda-Díaz

Abstract

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

Keywords: Antioxidants; Diabetes mellitus; Diabetic retinopathy; Nitrosative stress; Oxidative stress.

References

    1. Engerman R, Kern T. Hyperglucemia as a cause of retinopathy. Metabolism 1986;35:20–23. doi: 10.1016/0026-0495(86)90182-4
    1. Zhou ZJ, McCall MA. Retinal ganglion cells in diabetes. AM J Physiol 2008;586:4343–45. doi: 10.1113/jphysiol.2008.160838
    1. Kern TS, Tang J, Mizutani M, Kowluru RA, Nagaraj RH, Tomeo G, et al. . Response of capillary cell death to aminoguanidine predicts the development of retinopathy comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci 2000;41:3972–78.
    1. Lorenzi M. The polyol pathway as a mechanism for diabetic retinopathy: attractive elusive, and resilient. Exp Diabetes Res 2007;2007:1–10. doi: 10.1155/2007/61038
    1. El-Asrar AM. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol 2012;19(1):70–74. doi: 10.4103/0974-9233.92118
    1. Tiwari B, Pandey K, Abidi A, Rizvi S. Markers of oxidative stress during Diabetes mellitus. J Biomarkers 2013:1–8.
    1. Rodriguez A, Castellanos J, Martínez E, Miller G, Pacheco F, Miranda A, et al. . Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic retinopathy. J Diab 2014;6(2):167–75. doi: 10.1111/1753-0407.12076
    1. Guichardant M, Chantegrel B, Deshayes C, Doutheau A, Moliere P, Lagarde M. Specific markers of lipid peroxidation issued from n-3 and n-6 fatty acids. Biochem Soc Trans 2004;32(1):139–40. doi: 10.1042/bst0320139
    1. Kowluru R, Pooi-See C. Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007;2007:1–12.
    1. Wong T, Gillies M, Mohamed Q. Management of diabetic retinopathy a systematic review. JAMA 2007;298(8):902–16. doi: 10.1001/jama.298.8.902
    1. Claramunt J. Retinopatía diabetic. Rev Med Clin CONDES 2009;20(5):670–9.
    1. Bonakdar R, Guarneri E. Coenzyme Q10. Am Fam Physician 2005;72(6):1065–70.
    1. Crane F. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001;20(6):591–8. doi: 10.1080/07315724.2001.10719063
    1. Kieburtz K. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology 2007;68:20–28. doi: 10.1212/01.wnl.0000250355.28474.8e
    1. Potgleter M, Pretorius E, Pepper M. Primary and secondary coenzyme Q10 deficiency: the role of therapeutic suplementation. Nutr Rev 2013;7(3):180–8. doi: 10.1111/nure.12011
    1. Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets 2010;11(1):111–21. doi: 10.2174/138945010790031018
    1. Parisi V, Tedeschi M, Gallinaro G, Varano M, Saviano S, Piermarocchi S, CARMIS Study Group . Carotenoids and antioxidants in age-related maculopathy Italian study: multifocal electroretinogram modifications after 1 year. Ophthalmology 2008;115(2):324–33. doi: 10.1016/j.ophtha.2007.05.029
    1. Hernández-Ojeda J, Cardona-Muñoz EG, Román-Pintos LM, Troyo-Sanromán R, Ortiz-Lazareno PC, Cárdenas-Meza MA, et al. . The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study. J Diab Complicat 2012;26(4):352–8. doi: 10.1016/j.jdiacomp.2012.04.004
    1. Piermarocchi S, Saviano S, Parisi V, Tedeschi M, Panozzo G, Scarpa G, et al. . Carmis Study Group. Carotenoids in age-related maculopathy Italian Study (CARMIS): two-year results of a randomized study . Eur J Ophthalmol 2012;22(2):216–25. doi: 10.5301/ejo.5000069
    1. Standards of medical care in diabetes 2012. Diabetes Care 2012;35(1):S11–S63.
    1. Drozda J,Jr, Messer JV, Spertus J, Abramowitz B, Alexander K, Beam CT, et al. . ACCF/AHA/AMA-PCPI 2011 performance measures for adults with coronary artery disease and hypertension: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures and the American Medical Association-Physician Consortium for Performance Improvement. Circulation 2011;124(2):248–70. doi: 10.1161/CIR.0b013e31821d9ef2
    1. Wilkinson CP, Ferris FL, III, Klein RE, Lee PP, Agardh CD, Davis M, et al. . Global Diabetic Retinopathy Project Group. Proposed international diabetic retinopathy and diabetic macular edema disease severity scales . Ophthalmology 2003;110:1677–82. doi: 10.1016/S0161-6420(03)00475-5
    1. Lima V. Retinopatía diabética simplificada: la escala clínica internacional. Rev Hosp Jua Mex 2006;73(4):170–4.
    1. Early Treatment Diabetic Retinopathy Study Research Group . ETDRS report no. 3: Techniques for scatter and focal photocoagulation treatment of diabetic retinopathy . Int Ophthalmol Clin 1987;274:254–64.
    1. Asghar Ghasemi A, HedayatiII M, Biabani H. Protein precipitation methods evaluated for determination of serum nitric oxide end products by the Griess assay. JMSR 2007;2:29–32.
    1. Standards of Medical Care in Diabetes 2012. Diabetes Care 2012;35(1):S11–63.
    1. Park CY, Park SE, Bae JC, Kim WJ, Park SW, Ha MM, et al. . Prevalence of and risk factors for diabetic retinopathy in Koreans with type II diabetes: baseline characteristics of Seoul Metropolitan City-Diabetes Prevention Program (SMC-DPP) participants. Br J Ophthalmol 2012;96:151–5. doi: 10.1136/bjo.2010.198275
    1. Brauner H, Lüthje P, Grünler J, Ekberg NR, Dallner G, Brismar K, et al. . Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity. Clin Exp Immunol 2014;177(2):478–82. doi: 10.1111/cei.12316
    1. Eriksson JG, Forsén TJ, Mortensen SA, Rohde M. The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors 1999;9(2–4):315–8. doi: 10.1002/biof.5520090229
    1. Monnier L, Colette C, Owens DR. Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it? J Diabetes Sci Technol 2008;2(6):1094–1100. doi: 10.1177/193229680800200618
    1. Gupta M, Chari S. Lipid peroxidation and antioxidant status in patients with diabetic retinopathy. Indian J Physiol Pharmacol 2005;49(2):187–92.
    1. Guichardant M, Chantegrel B, Deshayes C, Doutheau A, Moliere P, Lagarde M. Specific markers of lipid peroxidation issued from n-3 and n-6 fatty acids. Biochem Soc Trans 2004;32(1):139–40. doi: 10.1042/bst0320139
    1. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11(1):81–128. doi: 10.1016/0891-5849(91)90192-6
    1. Njie-Mbye YF, Kulkarni-Chitnis M, Opere CA, Barrett A, Ohia SE. Lipid peroxidation: pathophysiological and pharmacological implications in the eye. Front Physiol 2013;4:366. doi: 10.3389/fphys.2013.00366
    1. Mancino R, Di Pierro D, Varesi C, Cerulli A, Feraco A, Cedrone C, et al. . Lipid peroxidation and total antioxidant capacity in vitreous, aqueous humor, and blood samples from patients with diabetic retinopathy. Mol Vis 2011;17:1298–304.
    1. Izumi N, Nagaoka T, Mori F, Sato E, Takahashi A, Yoshida A. Relation between plasma nitric oxide levels and diabetic retinopathy. Jpn J Ophthalmol 2006;50:465–8. doi: 10.1007/s10384-006-0344-y
    1. Doganay S, Evereklioglu C, Er H, Türköz Y, Sevinç A, Mehmet N, et al. . Comparison of serum NO, TNF-alpha, IL-1 beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye 2002;16:163–70. doi: 10.1038/sj/eye/6700095
    1. Castilho Á, Aveleira CA, Leal EC, Simões NF, Fernandes CR, Meirinhos RI, et al. . Heme oxygenase-1 protects retinal endothelial cells against high glucose- and oxidative/nitrosative stress-induced toxicity. PLoS One 2012;7(8):e42428. doi: 10.1371/journal.pone.0042428
    1. Leal EC, Manivannan A, Hosoya K, Terasaki T, Cunha-Vaz J, Ambrósio AF, et al. . Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest Ophthalmol Vis Sci 2007;48(11):5257–65. doi: 10.1167/iovs.07-0112
    1. Beyazyıldız E, Cankaya AB, Ergan E, Anayol MA, Ozdamar Y, Sezer S, et al. . Changes of total antioxidant capacity and total oxidant status of aqueous humor in diabetes patients and correlations with diabetic retinopathy. Int J Ophthalmol 2013;6(4):531–6.
    1. Valabhji J, McColl AJ, Richmond W, Schachter M, Rubens MB, Elkeles RS. Total antioxidant status and coronary artery calcification in type 1 diabetes. Diabetes Care 2001;24(9):1608–13. doi: 10.2337/diacare.24.9.1608
    1. Astaneie F, Afshari M, Mojtahedi A, Mostafalou S, Zamani MJ, Larijani B, et al. . Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients. Arch Med Res 2005;36(4):376–81. doi: 10.1016/j.arcmed.2005.03.007

Source: PubMed

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