Reference

Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats

Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats. Morley, Colin G. D.; Boyer, James L. (Dep. Med., Univ. Chicago, Chicago, Ill., USA). Biochim. Biophys. Acta, 477(2), 165-76 (English) 1977. CODEN: BBACAQ. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Rats treated with thioacetamide [62-55-5] undergo hepatocellular proliferation reminescent of liver regneration following partial hepatectomy. Thirty-six h after administration of 50 mg thioacetamide/kg body wt. to rats, [3H]thymidine incorporation into hepatic DNA reaches a peak of 78 .times. 103 dpm/mg DNA compared to a control of 3.2 .times. 103 dpm/mg DNA. Serum obtained from 6 to 48 h after administration of thioacetamide to rats stimulated hepatic but not kidney DNA synthesis in mice and rats. Autoradiog. revealed an increase in the incorporation of labeled thymidine into the nuclei of mouse hepatocytes. The mitotic index of the liver was also increased. The serum factor stimulating these changes in the liver was nondialyzable and heat stable. These results indicate that thioacetamide-induced liver injury results in a humoral factor which stimulates DNA synthesis in rat and mouse liver which has similar properties to a growth-stimulating factor previously identified in the serum from partially hepatectomized rats.

Thioacetamide-induced hepatic necrosis

Thioacetamide-induced hepatic necrosis. I. Involvement of the mixed-function oxidase enzyme system. Hunter, A. L.; Holscher, M. A.; Neal, R. A. (Cent. Enviorn. Toxicol., Vanderbilt Univ., Nashville, Tenn., USA). J. Pharmacol. Exp. Ther., 200(2), 439-48 (English) 1977. CODEN: JPETAB. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Thioacetamide [62-55-5] and one of its metabolites, thioacetamide sulfine [2669-09-2] were compared for their ability to inhibit hepatic mixed-function oxidase [9040-60-2] enzyme system as well as their ability to induce hepatic necrosis. Thioacetamide sulfine was found to decrease aminopyrine [58-15-1] N-demethylation and aniline [62-53-3] hydroxylation at a lower dose and at an earlier time after administration than was the case with thioacetamide. In addn., at all doses examd., thioacetamide sulfine produced a more severe centrilobular hepatic necrosis than equiv. doses of thioacetamide. To det. whether the hepatic mixed-function oxidase enzyme system was involved in the biotransformation of thioacetamide and/or thioacetamide sulfine to a hepatotoxic compd.(s), the severity of liver damage was examd. after the administration of an inducer or inhibitors of hepatic mixed-function oxidase enzyme activity. Phenobarbital pretreatment potentiated the hepatic necrosis produced by both thioacetamide and thioacetamide sulfine. In contrast, pyrazole, SKF 525-A, and cobaltous chloride protected against the hepatic necrosis caused by thioacetamide and thioacetamide sulfine. These data suggest that bot thioacetamide and thioacetamide sulfine are activated by hepatic mixed-function oxidase enzymes to a hepatotoxic compd.(s). These data also suggest that the hepatotoxicity of thioacetamide may be mediated by its metab. to thioacetamide sulfine which, in turn, is metabolized to an ultimate toxic metabolite.