The peroxisome proliferator-activated receptor-γ agonist pioglitazone protects against cisplatin-induced renal damage in mice

Peroxisome proliferator-activated receptor-g (PPAR-g) agonists not only improve metabolic abnormalities ofdiabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimentalmodels. Here, we investigated the effect of PPAR-g agonist pioglitazone against acute renal injury on a cisplatin modelin mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10mgkg –1 ). Pioglitazone wasadministered for six consecutive days in doses of 15 or 30mgkg –1 day –1 , per os (p.o.), starting 3days before cisplatin injection.Cisplatintreatmenttomiceinducedamarkedrenalfailure,characterizedbyasignificantincreaseinserumureaandcreatininelevels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levelsof non-enzymatic antioxidant defenses [glutathione (GSH) and as corbic acid levels] and components of the enzymatic antioxidantdefenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and andglutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against theincrease in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazoneadministration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protectedagainst the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These resultsindicated that pioglitazone has a protective effectagainstcisplatin-inducedrenal damagein mice.The protection ismediatedby preventing the decline of antioxidant status. The results have implications in use of PPAR-g agonists in human applicationfor protecting against drugs-induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.Keywords: peroxisome proliferator-activated receptor-g; pioglitazone; cisplatin; nephrotoxicity; mice