Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes

Abstract

The relationship was investigated between biochemical and morphological changes in chloroform (CHCl₃)- and carbon tetrachloride (CCl₄)-induced liver damage. The time courses of hepatic microsomal cytochrome P450 (CYP) content, hepatic microsomal CYP2E1 activity, hepatic reduced glutathione (GSH) content, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were examined in relation to the liver morphology in rats orally treated with CHCl₃ or CCl₄ (3.35 mmol/kg). The CYP content and the activity of CYP2E1 markedly decreased in the CCl₄-treated rats 3 h after treatment compared to much lower decreases in the CHCl₃-treated rats. The hepatic GSH content was decreased to a similar extent in both groups of rats at 3 h after treatment; in the CCl₄-treated rats, the GSH content continued to decrease, reaching a minimum at 24 h and without attaining the normal level at 72 h after treatment. By contrast, hepatic GSH content in the CHCl₃-treated rats began to increase from 6 h, attaining complete recovery 48 h after treatment. Plasma ALT and AST activities were significantly elevated by CCl₄ as early as 3 h after treatment, while the activities in the CHCl₃-treated rats did not increase until 6 h after treatment. In both groups of rats, ALT and AST activities reached a maximum at 24 h, and gradually decreased, remaining at abnormal levels at 72 h. Hepatic cells in the CCl₄-treated rats were found to be necrotic as early as 3 h post-treatment, whereas few or no morphological changes appeared in the liver of CHCl₃-treated rats. The extent of necrosis was at a maximum 24 h after treatment in both CHCl₃- and CCl₄-treated rats. In addition, some necrotic cells remained in the liver of CCl₄-treated rats 72 h after treatment, while the necrosis in the CHCl₃-treated rats was almost negligible. The present results indicate that almost the same time-courses of biochemical and morphological changes were followed in rats of both the CHCl₃- and CCl₄-treated groups.