title: The peroxisome proliferator-activated receptor-γ agonist pioglitazone protects against cisplatin-induced renal damage in mice.
abstract: Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas - LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
authors.forename: Cristiani F
authors.initials: CF
authors.lastname: Bortolatto
authors.forename: Ethel A
authors.initials: EA
authors.lastname: Wilhelm
authors.forename: Silvane Souza
authors.initials: SS
authors.lastname: Roman
authors.forename: Marina
authors.initials: M
authors.lastname: Prigol
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D020011:Protective Agents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D020011:Protective Agents; D045162:Thiazolidinediones; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid; D002945:Cisplatin; D000077205:Pioglitazone