ABSTRACT
PURPOSE: This study investigated the effect of reducing cisplatin induced nephrotoxicity with DWP-04 that is the compound of Schizandrin C derivative biphenyldimethyl dicarboxylate (DDB), glutathione and selenium. For the purpose of observation is that how DWP-04 has influence on mechanism of reducing cisplatin induced nephrotoxicity with renal function test, free radical formation and detoxification enzyme system in renal tissue. METHODS: Five groups of rats were dosed with vehicle, cisplatin (2 mg/kg i.p.), cisplatin+DWP-04 (100, 200 mg/kg po), or cisplatin+sodium thiosulfate (200 mg/kg i.p.) daily for 4 weeks. RESULTS: Serum creatinine, lactate dehydrogenase and activity of hydroxy radical increased in the cisplatin group and suppressed in the cisplatin+DWP-04 group compared to the cisplatin group. The renal tissue concentration of lipid peroxidase and lipofuscin were increased in the cisplatin group compared to the other groups. The activity of aminopyrine N-demethylase, aniline hydroxylase, aldehyde oxidase and xanthine oxidase, of which free radical formation system in kidney was also decreased in the cisplatin+DWP-04 group compared to the cisplatin and cisplatin+sodium thiosulfate group. The activity of detoxification system of free radical, such as glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were markedly increased in the cisplatin+DWP-04 group than the cisplatin and the cisplatin+sodium thiosulfate group (p<0.05). CONCLUSION: It can be concluded that the mechanism of decreasing cisplatin-induced nephrotoxicity by DWP-04 is that the decreasing of the amount of lipid peroxide and lipofuscin in the renal tissue by increasing activity of the antioxidant defense system and the decreasing of reactive oxygen species by increasing detoxification enzyme activity.