RESUMO
AIM: To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes. METHODS: For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 mumol/L, 3 mumol/L, 5 mumol/L and 10 mumol/L) and in combination with CCl(4) (86 mumol/L). The cells were also pretreated with 14 mumol/L amiodarone and then the other two compounds were added. RESULTS: Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl(4)induced the expected severe damage on the examined parameters. CCl(4) induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin. CONCLUSION: We suggest that the observed cytoprotective effect was due to interactions between lovastatin, CCl(4) and amiodarone at a metabolic level.
