The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

Abstract

Cisplatin (CP) is an important platinum-based chemotherapy agent widely used to treat solid tumors. However, nephrotoxicity is the main limiting adverse effect in 25%–35% of patients treated with even a single dose of CP. This study aimed to evaluate the role of liraglutide (LIRA) and alfacalcidol (ALFA), each of them alone and in combination, in prevention of CP-induced nephrotoxicity. Forty male albino mice were divided into five groups including normal control group and groups CP, CP with LIRA, CP with ALFA, or CP with LIRA and ALFA. Nephrotoxicity was induced by single intraperitoneal injection of CP in a dose 12mg/kg. LIRA and/or ALFA treatment was started 5 days before induction of nephrotoxicity and continued till the end of experiment. Kidney function tests, oxidative stress and ferroptosis parameters were assessed. Histopathological and immunohistochemical examination were performed on kidney tissues. Both LIRA and ALFA monotherapy resulted in a significant improvement in kidney function tests, increased antioxidant levels, inhibition of ferroptosis and improved histopathological findings. LIRA showed more improvement compared to ALFA and their combination showed better results than each one alone. In conclusion, LIRA and ALFA either alone or in combination, represent a promising preventive modality for amelioration of CP-induced nephrotoxicity.