Protective effects of glutathione on cisplatin-induced toxicity to rat hepatocytes

Objective To investigate the effects of glutathione on cisplatin-induced toxicity to rat hepatocytes.Methods Hepatocytes were isolated from rats and then inoculated into 96 well plates,after pretreatment of L-cysteine(precursor of GSH synthesis) or BSO(inhibitor of GSH synthesis)for 4 hours and 16 hours,respsectively.A series of concentrations of cisplatin,in the presence and absence of L-cysteine,were added and coincubated,MTT assays were performed to test cell viability at 8,24 or 48 hours after coincubation.Results Cisplatin had time-dependent and concentration-dependent cytotoxicity.The concentrations of cisplatin that inhibited 50% cell growth(IC 50) of rat hepatocytes at 8,24 and 48 hours were 1 13,0.21 and 0.15mmol/L,respectively.BSO made IC 50 of cisplatin to rat hepatocytes lower down to 0.017,0.011 and 0 013mol/L,respectively,while L-cysteine made IC 50 increase up to more than 5mmol/L.Conclusion Cisplatin has time and concentration-dependent toxicity to rat hepatocytes;BSO can enhance cisplatin-induced cytotoxicity,while L-cysteine can protect cisplatin-induced cytotoxicity.It was possible that GSH can protect cisplatin-induced toxicity to rat hepatocytes.