Rapid depression of rat liver microsomal calcium pump activity after administration of carbon tetrachloride or bromotrichloromethane and lack of effect after ethanol

Abstract

Calcium sequestration was studied in microsomes prepared from the livers of rats given acute doses of carbon tetrachloride (CCl 4), bromotrichloromethane (BrCCl 3), or ethanol. Hepatic mitochondrial calcium uptake was also studied in ethanol-treated animals. The effects of dose and time are reported. It was found that a dose of 6 g ethanol/kg had no effect on either microsomal or mitochondrial calcium uptake during the first 20 hr after administration. After administration of 1.0–5.0 ml CCl 4/kg, calcium uptake was reduced 85% from controls in 10 min, and 3 min after administration of 2.5 ml BrCCl 3/kg calcium uptake was reduced 90% from controls. The inhibition of microsomal calcium uptake occurred at the same time as the appearance of microsomal lipid diene conjugates and slightly after the maximal incorporation of 14C from 14CCl 4 into rat liver microsomal lipids, as reported by K. S. Rao and R. O. Recknagel [(1968). Exp. Mol. Pathol. 9, 271–278; (1969) . Exp. Mol. Pathol. 10, 219–228]. Decreased microsomal calcium pumping is one of the earliest signs of CCl 4 or BrCCl 3 hepatotoxicity. This finding supports the proposal that an early disturbance of calcium uptake may contribute to the chain of events leading from localized toxigenic haloalkane metabolism to the metabolic disorganization eventuating in cell death. The complete absence of any effects of acute ethanol administration on microsomal or mitochondrial calcium pump activity suggests that liver injury by ethanol does not involve lipid peroxidation in these organelles.