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(IC₅₀)of rathepatocytes at 8, 24 and 48 hours were 1.13, 0.21 and 0.15 mmol/L, respectively.BSO made IC₅₀ of cisplatin to rathepatocytes lower down to 0.017, 0.011 and 0.013 mol/L, respectively, while L-cysteine made IC₅₀ increase up to more than 5 mmol/L.

  Conclusion   Cisplatin has time and concentration-dependent toxicity to rathepatocytes; 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 rathepatocytes.