Study on nephroprotective effect of Ebselen in cisplatin induced renal damage in rats

Background: Renal dysfunction arises as a result of exposure to medicines, industrial or environmental chemicals. Cisplatin is a major antineoplastic drug used for the treatment of solid tumors. Its chief dose limiting side effect is nephrotoxicity; 20% of patients receiving high-dose cisplatin have severe renal dysfunction. Ebselen a promising antioxidant, was used to explore the nephroprotective effect.Methods: The rats were divided into five groups; each group consisting of 6 animals. The experimental design included one control group and four experimental groups. The study was carried out for a period of 7 wks. The test drug Ebselen in group 4 and 5 and the reference standard drug Amifostine in group 3 was administered once a week intraperitoneally for 5 weeks. Nephrotoxicity was induced by cisplatin (5mg/kg IP) in the 6th week, following this the drug Amifostine in group 3 and Ebselen in group 4 and 5 will be continued twice a day for 5 consecutive days post induction. Urine samples were collected and sent for determination of urine creatinine and albumin.Results: The Urine creatinine level and albumin level estimation in group II show significant renal damage as compared to control group. The statistical reduction in urine creatinine and urine albumin level in Ebselen treated group I (10mg/kg), Ebselen group V (20mg/kg) as compared to Cisplatin group II show a potential reduction in renal damage. Ebselen treated group V showed a reduction in urine creatinine and urine albumin as same as in group III.Conclusions: This study brings to a close that Ebselen lessens Cisplatin induced renal damage

ROLE OF EBSELEN, A SELENOORGANO COMPOUND IN CISPLATIN INDUCED NEPHROTOXICITY IN WISTAR RATS

Objective: Nephrotoxicity is encountered worldwide, irrespective of several factors, but drug induced nephrotoxicity is a complication that is attributed to the high dose and even low dose of drugs. Cisplatin, a platinum complex used in the chemotherapy of several solid tumors was found to have a chief dose limiting side effect namely nephrotoxicity, which occurred due to lipid peroxidation and formation of reactive oxygen species. Ebselen, a eleno organo compound, a glutathione peroxidase mimic with anti-oxidant activity was used in our study to evaluate its nephro protective potential. Methods: Male wistar rats, 6-8 wks old, weighing 180-200 grams were used for the study, which was carried out for a period of 7 wks. Animals were divided into five groups; each group consisting of 6 animals. Group I served as control. Group IV & V received the test drug Ebselen in doses of 10 mg/kg & 20 mg/kg respectively. Group III received Amifostine at 50 mg/kg. The drugs were administered once a week intraperitoneally for 5 wks. Nephrotoxicity was induced at a dose of 5 mg/kg single dose for groups II to V in the 6th wk and the drugs in group III, IV & V continued for 5 days post induction. In the 7th wk blood samples were collected for biochemical analysis and kidney tissues for histopathological study. Results: The serum urea, creatinine levels were significantly increased in Cisplatin group compared to other groups. The estimation of antioxidant levels (catalase, superoxide dismutase and glutathione peroxidise) was significantly decreased in cisplatin group and increased in other groups. The estimation of Malondialdehyde an indicator of lipid peroxidation was significantly increased in group II and decreased in drug treated group. Histopathology results of animals treated with Cisplatin showed inflammatory changes such as tubular degeneration, edema, and necrosis, infiltration of cells in tubular interstitum, mild intertubular hemorrhage and atrophy of glomeruli which was severe in group II. Some changes were also observed in Group III, IV and V animals but with less severity. Conclusion: The result of our study effectively proves the antioxidant potential of Ebselen in ameliorating Cisplatin induced nephrotoxicity