Investigation of the protective effect of escin on cisplatin induced nephrotoxicity in rats.

Cisplatin is one of the most effective antineoplastic drugs used in human and veterinary medicine. Altough cisplatin is an important drug in cancer chemotherapy, its side effects such as nephrotoxicity, hepatotoxicity and neurotoxicity limit the use of cisplatin. Escin is a triterpenoid which is obtained from the horse chestnut plant and have antioxidant, anti-inflammatory and anticancer effect. In our study, it was aimed to examine the protective effect of escin against cisplatin toxicity, mainly nephrotoxicity. Within the scope of the study, 40 Wistar albino rats were divided into 4 groups, 10 in each group. The groups were divided into 4 groups as control, cisplatin, escin, and escin+cisplatin. Intraperitoneal (i.p.) saline administration was applied to the control group for 6 days. A single dose of 7,5 mg/kg cisplatin was administered intraperitoneally to the cisplatin group on the 4th day. Escin group was administered 3,6 mg/kg of escin for 6 days. Escin+cisplatin group was intraperitoneally administered 3,6 mg/kg escin for 6 days and on the 4th day of escin administration, a single dose of 7,5 mg/kg cisplatin.At the end of the study, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TB) levels were analyzed in serum samples taken from the rats. Moreover, superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were determined spectrophotometrically in kidney, liver and brain tissues. Kidney, liver, brain, cerebellum and hippocampus tissues were examined histopathologically by hematoxylin-eosin staining as well as immunohistochemically for interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and caspase-3 expression. As a result of the study, it was determined that cisplatin increased urea, creatinine, AST, ALT and TB levels, and this increase was accompanied by MDA.It has been observed that the administration of cisplatin with escin increased urea, creatinine, AST, ALT and TB levels similar to cisplatin, this situation accompanied by MDA and even caused a higher increase in AST and ALT levels than the cisplatin administered group. However, SOD and GPx levels were found to be higher in the escin+cisplatin administered group than in the cisplatin administered group alone. Consistent with the organ damage observed in the histopathological findings, serum biochemical parameters and MDA level, the use of escin and cisplatin caused more damage to the specified tissues than the use of cisplatin alone. Similarly, IL-1β, iNOS, and caspase-3 immunoreactivity increased with cisplatin administration, and escin administration with cisplatin caused more immunoreactivity than cisplatin alone. As a result, it was observed that escin administration increased hepatotoxicity and neurotoxicity, mainly nephrotoxicity caused by cisplatin, and the reason for this was apoptosis and inflammation related to caspase. It was concluded that when escine is used together with cisplatin, it increases cytokine levels, and accordingly, it promotes iNOS release and apoptosis, and it has synergistic toxicity rather than a protective effect through this pathway.