Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice

Rosmarinic acid (RA) is a natural phenolic compound with a broad range of applications, from food preservatives to cosmetics. Increasing amounts of evidence suggests its beneficial effects against various pathological conditions. The aim of this study was to investigate the therapeutic activity of rosmarinic acid (RA) against cisplatin (CP)-induced nephrotoxicity. RA was administered by oral gavage at doses of 1, 2 and 5 mg/kg for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Twenty four hours later, mice were sacrificed. Treatment with RA significantly ameliorated histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP. Oxidative stress induced by CP, evidenced by increased renal 4-hydroxynonenal (4-HNE), cytochrome P450 2E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced by RA administration. Moreover, RA inhibited the expression of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-α (TNF-α), indicating the inhibition of inflammation. Additionally, RA exhibited antiapoptotic activity through the reduction of p53, phosphorylated p53 and active caspase-3 expression in the kidneys. These findings show that RA ameliorates CP-induced oxidative stress, inflammation and apoptosis in the kidneys. The nephroprotective activity of RA could be, at least in part, attributed to reduced CYP2E1 expression.