Dose-dependent liver tissue repair in chloroform plus thioacetamide acute hepatotoxicity

The objective of this study was to test whether a binary mixture (BM) of chloroform (CHCl3) and thioacetamide (TA) causes a dose-dependent liver injury and an opposing tissue repair. Liver injury was assessed by plasma alanine aminotransferase (ALT) and histopathology. Tissue repair was measured by [H-3-CH3]-thymidine (H-3-T) incorporation into hepatonuclear DNA and PCNA over a time course of 0-72 h. Male Sprague-Dawley (S-D) rats received six- and five-fold dose ranges of TA and CHCl3, respectively. ALT levels and 3 H-T incorporation were in complete agreement with corresponding microscopic observations, and only ALT elevation and 3 H-T incorporation data are presented here. Liver injury observed after exposure to BM was no different than addition of injuries caused by individual compounds. Tissue repair was prompt and adequate, leading to recovery from injury and animal survival. Tissue repair is dose-dependent and plays central role in the hepatotoxic outcome. (C) 2004 Elsevier B.V. All rights reserved.