Protective effects of benfotiamine in the experimentally-induced nephrotoxicity with cisplatin in rabbits

ABSTRACT

Cell death is the component of many response patterns of living tissues to xenobiotics including cytotoxic drugs, and one of the possible ways to ameliorate this response is through interference with the process of apoptosis which can be fulfilled by many candidate substances like benfotiamine. This study was designed to evaluate the possible cytoprotective effect of orally administered benfotiamine against cisplatin -induced nephrotoxicity in rabbits. Twenty adult rabbits are used in this study and allocated into 4 groups; treated as follow Saline treated as controls, cisplatin [2.5mg/kg] treated group; benfotiamine [70mg/kg] seven days before and during cisplatin treatment and thiamine [70mg/kg] treated rabbits. At the end of treatment all animals are sacrificed, serum and kidney tissue homogenate are prepared for the assay of urea, creatinine, uric acid and thiamine in the serum; malondialdehyde [MDA], glutathione [GSH] and thiamine levels in kidney tissue homogenate. Kidney tissue sections are prepared for histological examination. Benfotiamine treatment resulted in ameliorating the nephrotoxicity induced by cisplatin as evidenced by lowering serum urea and creatinine levels, while uric acid was not affected. Concerning the effect on oxidative stress parameters; MDA levels in tissue homogenate were significantly reduced while GSH levels not improved significantly. Histological evidences supported the biochemical parameters which indicate nephroprotective effect of Benfotiamine. The orally administered prodrug elevates thiamine levels in kidney tissue homogenate many fold greater than those produced by conventional thiamine. According to the results obtained in this study one can conclude that benfotiamine has the ability, through a mechanism not related to direct antioxidant property, to provide cytoprotective effects against drug-induced nephrotoxicity; and might be a good candidate to be tried experimentally and clinically in this respect