[Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats]

Abstract

This study examined whether nifedipine or flunarizine, calcium channel blockers, could protect the liver against halothane hepatotoxicity in rats. Six groups of 102 enzyme-induced male Sprague-Dawley rats were studied. Group N1 and N2 rats received nifedipine 20 micrograms and 100 micrograms.kg-1.day-1, and group F1 and F2 rats received flunarizine 100 micrograms and 1mg.kg-1.day-1 in their drinking water for 24 hours prior to the experiment. They were then anesthetized with N2-O2-halothane 0.5% under the condition of hypoxia (FIO2 0.12) for two hours. Animals in group H were given clear water, and then anesthetized with halothane and hypoxia. Animals in group C were given clear water and exposed to hypoxia alone. Twenty-four hours after anesthesia, all animals were decapitated and their liver specimens were stained with H&E for the examination by light microscopy. Eighty percent of rats in group H showed centrilobular degeneration, but administration of nifedipine or flunarizine reduced the incidence significantly. Furthermore, histological score graded from 0 to 3, according to the degree of centrilobular degeneration was also significantly reduced by administration of nifedipine or flunarizine. These results suggest that oral administration of nifedipine or flunarizine could prevent the incidence of halothane-induced hepatotoxicity in enzyme-induced rats, probably by preventing the increase in cytosolic calcium concentration.