Carbon Tetrachloride Induced Calcium Accumulation in Rat Liver

Carbon tetrachloride (CCl4下) induces steatosis, calcium accumulation and necrosis in rat liver. It has been clarified that fat accumulation is independent of necrosis. However, the mechanism of calcium accumulation and the role of increased calcium in CCｌ4下 hepatotoxicity are obscure. The present study was undertaken to resolve the above problems. The results are summarized as follows. 1) After the administration of CCl4下 (2.5 m//kg, p. o.), a transient increase, twice of normal level, of hepatic calcium at 2 hours (hrs) was observed prior to the marked increase of it at 24 hrs. However the increase of serum calcium level was detected only at 2 hrs. The hepatic calcium content at 24 hrs was ten-fold that of normal liver, and both mitochondrial and microsomal calcium increased at this time, while at 2 hrs only mitochondrial calcium increased. The TBA values in two subcellular fractions increased at 2 hrs, then were maintained at the same level at 24 hrs. No hepatic dysfunction was detected by several function test at 2 hrs. 2) While pretreatment with a small dose of CCl4下 (0.25 m//kg) inhibited microsomal calcium accumula-tion, the increase of TBA values in subcellular fractions by 2.5 m//kg of CCl4下 was seen. Pretreatment with N, N'-diphenyl-p-phenylenediamine (600 mg/kg, three times) inhibited both CCl4下-induced increases of microsomal calcium and TBA values. Pretreatment with lanthanum chloride (2 g/kg) inhibited the calcium accumulation in two subcellular fractions but not lipid peroxidation of microsomal fraction. The pretreatments except for lanthanum chloride inhibited CCl4下-induced hepatic dysfunction. From the above results, it seems likely that the cause for CCl4下-induced calcium accumulation in liver may be different between its early stage and its late stage, and that the increase of microsomal and/or cytosol calcium may play an important role for hepatic necrosis