Studies on the mechanism of enhancement of carbon tetrachloride hepatotoxicity by Triton WR 1339.

Pretreatment of rats with Triton WR 1339 significantly enhanced the intensity of CC14-induced liver necrosis. Previous workers suggested that this effect might be due to enhancement by Triton WR 1339 of cellular degradative processes. This pretreatment, however, also enhanced the intensity of covalent binding of [14C]CC14 metabolites to microsomal protein at 3 or 6 h, but not 1 h after its administration. This effect is not due to changes of microsomal P-450 content or increased activity of mixed-function oxygenase-metabolizing drugs like pentobarbital. Pretreatment with Triton WR 1339 also partially increased CC14-induced peroxidation of microsomal lipids at 1, 3 or 6 h after administration of the hepatotoxin. Liver concentrations of CC14 in Triton WR 1339-treated rats were significantly higher at 3 or 6 h but not at 1, 10 or 24 after its i.p. administration. Triton WR 1339 treatment decreased the body temperature of the rats and further intensified the decrease produced by CC14. Results suggest that, in addition to possible effects of Triton WR 1339 administration on liver-cell degradative processes, there are other actions of this detergent on CC14 activation and lipid peroxidation which might play a role in the heightened response of the liver of CC14-induced injury.