Effect of lithium on cyclosporin induced nephrotoxicity in rats

Psychoactive drugs provide essential intervention in the care of transplant recipients, yet little is known of their interaction with immunosuppressan ts such as cyclosporin (CSA). Lithium (Li) is an invaluable drug for the tr eatment of manic disorders in organ transplant patients. As both these drug s are known to produce renal toxicity, the concomitant use of CSA and Li ma y be potentially harmful. The present study was undertaken to investigate t he effect of CSA and Li chloride individually and in combination on renal s tructure and function of rats. Male Sprague-Dawley rats were divided into t he following eight groups of seven animals each: group 1, control (vehicle only); group 2, Li (2mEq/kg i.p.) alone; group 3, CSA 12.5mg/kg (subcutaneo us); group 4, CSA 25 mg/kg; group 5, CSA 50 mg/kg; group 6, CSA 12.5 mg/kg + Li; group 7, CSA 25 mg/kg + Li; and group 8, CSA 50 mg/kg + Li. The drugs were given once a day for seven days; Li being administered 30 min before CSA. Twenty four hours after the last dose of drugs the animals were sacrif iced and blood samples were analyzed for blood urea nitrogen (BUN), serum c reatinine (SCr), CSA and Li levels. The left kidney was analyzed for malond ialdehyde (MDA) and conjugated dienes (CD) levels and right kidney was used for histopathological studies. Our results showed that Li alone did not pr oduce any significant renal toxicity, whereas CSA dose dependently caused s tructural and functional changes in kidneys. However, significantly higher structural and functional impairment was observed in the animals treated wi th Li plus CSA as compared to CSA alone treated animals. Several fold incre ase in blood Li level was also noticed in the rats concomitantly treated wi th CSA and Li. A significant increase in MDA and CD in the rats treated wit h CSA plus Li suggests the role of oxidative stress in drug induced nephrot oxicity. These findings clearly demonstrate that even non toxic doses of Li may significantly exacerbate CSA induced nephrotoxicity in rats. The enhan ced nephrotoxicity following concomitant use of these drugs may be attribut ed to significant increase in the bioavailability of Li and enhanced oxidat ive stress. Further clinical studies are warranted to investigate the inter action of these nephrotoxic drugs in human subjects.