The aim of this study was to evaluate whether the antioxidant C-phycocyanin (C-PC, 5-30 mg kg(-1) i.p.) was able to prevent cisplatin (CP, 18 mg kg(-1) i.p.) induced nephrotoxicity by reducing oxidative stress in CD-1 mice. Nephrotoxicity was assessed by measuring blood urea nitrogen, plasma glutathione peroxidase, plasma creatinine, the renal activity of N-acetyl-β-d-glucosaminidase, apoptosis and histopathological changes. Oxidative stress was evaluated by measuring the content of glutathione, malondialdehyde, 4-hydroxynonenal and oxidized proteins in renal tissue. C-PC prevented CP-induced renal damage and oxidative stress in a dose-dependent manner. Moreover, C-PC prevented the decrease in the renal activity of the antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase induced by cisplatin. In vitro assays showed that C-PC was an effective scavenger of the following reactive species: hypochlorous acid, peroxynitrite anions, peroxyl radicals, diphenyl-1-picrylhydrazyl, hydroxyl radicals, superoxide anions, singlet oxygen and hydrogen peroxide. It is concluded that the protective effect of the nutraceutical C-PC against CP-induced nephrotoxicity was associated with the attenuation of oxidative stress and the preservation of the activity of antioxidant enzymes.

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The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

It has been shown that curcumin (CUR), a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

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