Protective effects of ligustrazine on cisplatin-induced oxidative stress, apoptosis and nephrotoxicity in rats

Cisplatin is an effective agent against various solid tumors. However, its nephrotoxicity been reported to be a dose-limiting factor for treating various types of tumors. The aim of this study was to determine the protective effects of ligustrazine on cisplatin-induced nephrotoxicity through tissue oxidant/antioxidant parameters, light microscopic evaluation, and tubular apoptosis in rats. Ligustrazine was administered in doses of 50 and 100 mg/kg/day intraperitoneally (i.p.), for 7 consecutive days, starting 2 days before a single intraveneous dose of cisplatin (8 mg/kg). Results revealed that treatment with cisplatin alone caused significant changes in the levels of urinary protein, urinary N-acetyl-beta-d-glucosaminidase, serum creatinine, blood urea nitrogen, and kidneys histopathological damages. All the aforementioned changes were effectively attenuated by ligustrazine. In addition, cisplatin caused increases in the levels of malondialdehyde, nitric oxide, nitric oxide synthase and decreases in the levels of reduced glutathione, glutathione-S-transferase, superoxide dismutase. These changes were restored to near normal levels by ligustrazine at 100 mg/kg. In conclusion, ligustrazine has dose dependent protective effects against cisplatin-induced renal tubular toxicity.