Attenuation of cisplatin�induced nephrotoxicity by p-coumaric acid through peroxisome proliferator-activated receptor-gamma (PPAR-?) agonism in male rats

Abstract

The objective of this study was to examine the role of peroxisome proliferator-activated receptor-gamma (PPAR-?) in renal protection provided by p-Coumaric acid in cisplatin induced nephrotoxicity in male rats. Single dose of cisplatin 5mg/kg (i.p.) was used to induce nephrotoxicity on first day of the study. The nephrotoxicity was evaluated by quantifying serum creatinine, creatinine clearance, urea, uric acid, potassium, magnesium, microproteinuria, fractional excretion of sodium. Superoxide anion generation, thiobarbituric acid reactive substances, myeloperoxidase activity and reduced glutathione levels were measured to assess oxidative stress in renal tissues whereas; hematoxylin eosin stain demonstrated renal histological changes. The nephrotoxicity was confirmed by the elevated level of urinary and blood parameters, increased parameters of oxidative stress as well as from the histopathological studies of kidney. Different doses of p-Coumaric acid (50 and 100mg/kg, p.o.) significantly (p<0.05) attenuated the various parameters associated with the nephrotoxicity. Moreover, the effect was found to be dose dependent. The nephroprotective effect of p-Coumaric acid was abolished by BADGE (30mg/kg, i.p.), (a PPAR-? inhibitor) pretreatment in rats. It may be concluded that p-Coumaric acid produced nephroprotection via PPAR-? agonism.