Renoprotective effect of the antioxidant curcumin: Recent findings

Abstract

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

Keywords: Bifunctional antioxidant; Mitochondrial dysfunction; Nephrotoxicity; Nrf2; Oxidative stress; Renal hemodynamics.

Figures

Fig. 1

Chemical structures and abundance of curcuminoids in turmeric that have terapeutic effects.

Fig. 2

Curcumin prevents renal hemodynamic alterations. Curcumin ameliorates 5/6NX-induced alterations in mean arterial pressure (MAP), proteinuria and glomerular filtration rate (GFR) and in the following parameters of renal hemodynamics: single-nephron glomerular filtration rate (SNGFR), single-nephron plasma flow (Qa), glomerular capillary pressure (PGc), afferent resistance (AR) and efferent resistance (ER).

Fig. 3

Curcumin is able to prevent mitochondrial dysfunction associated to renal injury. Curcumin is able to prevent lipid peroxidation and the decrease in the following mitochondrial determinations: oxygen consumption, activity of complexes I, II, II-III and V, activity of aconitase and antioxidant enzymes, GSH content, membrane potential, calcium retention and ATP content . GSH (Glutathione), SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase), GST (glutathione-S-transferase), GR (glutathione reductase), NAD+ (nicotinamide adenine dinucleotide), NADH (nicotinamide adenine dinucleotide, reduced form), FAD+ (flavin adenine dinucleotide), FADH2 (flavin adenine dinucleotide, reduced form), ATP (adenosine triphosphate), ADP (adenosine diphosphate).

Fig. 4

Curcumin is able to prevent several mechanisms leading to renal injury. Curcumin renoprotective effects have been associated with the prevention of three main factors, first the reduction of oxidative stress by (a) preventing the generation of O2−∙ and scavenging different reactive oxygen species, and (b) by preventing the Nrf2 degradation by ubiquitin proteosoma pathway, thus an increase of many antioxidant enzymes. Curcumin has been shown also to be able to reduce inflammatory process by reducing the inflammatory transcription factors such as NF- κB and TNF-α. On the other hand the reduction of cytokines such as TGF-β or CTGF eventually prevents a fibrotic process. ROS (reactive oxygen species), O2-∙ (superoxide),∙OH (hydroxyl radical), H2O2 (hydrogen peroxide), ONOO− (Peroxynitrite), 1O2 (Singlet oxygen), NO∙ (Nitric oxide), ROO∙ (peroxyl radical), Nrf2 (translocation of nuclear factor erythroid-derived 2), ARE (Antioxidant responsive elements), Keap1 (Kelch-like ECH-associated protein 1), Cul3 (cullin 3), Nedd8 (Neural precursor cell expressed developmentally down-regulated 8), u (ubiquitin), SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase), GST (glutathione-S-transferase), GCL (glutathione-cystein-ligase), TrX (thioredoxin), TGF-β (factor transforming growth beta), CTGF (connective tissue growth factor), NF- κB (nuclear factor kappa-light-chain-enhancer of activated B cells), TNF-α (tumor necrosis factor), PKC (protein kinase C), PI3K (phosphoinositol 3-kinase), PERK (protein kinase RNA-like endoplasmic reticulum kinase) MAPK (mitogen-activated protein kinase), CK2 (Casein kinase2).