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In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes

World Journal of Gastroenterology 2007年第15期13卷 2198-2204页

作者： AZ Krasteva MK Mitcheva MS Kondeva-Burdina va descatoire Laboratory of Toxicology and Drug metabolism Department of Pharmacology and Toxicology Faculty of PharmacyMedical UniversitySofiaBulgaria Faculty of Medicine Xavier Bichat INSERM U 481 Hopital Bichat16 rue Henri Huchard75018 ParisFrance

AIM： To investigate the interactions at a metabolic level between Iovastatin, 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 （1μmol/L, 3μmol/L, 5μmol/L and 10μmol/L） and in combination with CCh （86μmol/L）. The cells were also pretreated with 14μmol/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 840, respectively, LDH- activity increased by 114% and TBARS content by 90%, CCl4 induced the expected severe damage on the examined parameters, CCh induced toxicity was attenuated after Iovastatin 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 Iovastatin. CONCLUSION： We suggest that the observed cytoprotective effect was due to interactions between Iovastatin, CCh and amiodarone at a metabolic level.

关键词： Hepatocytes Lovastatin Carbon tetrachloride Amiodarone Interaction

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