Mechanism of chlorpromazine prevention of carbon tetrachloride-induced liver necrosis

Abstract

Chlorpromazine (CPZ) is able to partially prevent the CCl 4-induced liver necrosis in rats 24 hr but not 72 hr after its administration. Preventive effects at 24 hr were still observed when CPZ was given as late as 10 hr after CCl 4. Prevention is not due to variation in CCl 4 concentration in liver. CPZ does not decrease either the covalent binding of CCl 4 reactive metabolites to cellular constituents or lipid peroxidation but causes a marked decrease in the body temperature of the rats. Our results indicate that CPZ only delays the onset of necrosis and suggest that this effect is mediated by the CPZ decreasing effects on body temperature, since the necrosis observed in the CPZ-treated animals injected with CCl 4 and maintained at 37°C is as intense as that observed in the group receiving CCl 4 alone.