Explicit role of peroxisome proliferator-activated receptor gamma in gallic acid-mediated protection against ischemia-reperfusion-induced acute kidney injury in rats.

ABSTRACT

BACKGROUND: Gallic acid is a polyphenolic compound and is reported to be renoprotective because of its antioxidant activity in various preclinical studies. Gallic acid has been reported to activate peroxisome proliferator-activated receptor gamma (PPAR-γ) in vitro. However, the relevance of the interplay between gallic acid and PPAR-γ in various pathologic conditions is yet to be established in vivo. The present study investigated the protective role of gallic acid against ischemia-reperfusion-induced acute kidney injury (AKI) and the possible involvement of PPAR-γ in gallic acid-mediated renoprotection. MATERIALS AND METHODS: The AKI was induced in rats through bilateral clamping of renal arteries for 40 min followed by reperfusion for 24 h. The AKI was assessed by the quantification of creatinine clearance, blood urea nitrogen, uric acid, potassium level, fractional excretion of sodium, and urinary microproteins. The oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. The histopathologic changes in renal tissues were assessed by hemotoxylin and eosin staining. The rats were administered gallic acid (50, 100, and 200 mg/kg) orally for 7 d before subjecting them to AKI. RESULTS: The renal ischemia-reperfusion induced significant changes in plasma, urinary, and tissue parameters. The administration of gallic acid at three dose levels offered a significant protection against renal ischemia-reperfusion-induced AKI. The prior treatment with PPAR-γ antagonist, bisphenol A diglycidyl ether, significantly abolished the renoprotective effect of gallic acid that confirms the involvement of PPAR-γ in gallic acid-mediated renoprotection. CONCLUSIONS: It is concluded that the activation of PPAR-γ significantly contributes toward gallic acid-mediated protection against ischemia-reperfusion-induced AKI.