Tissue repair plays pivotal role in final outcome of liver injury following chloroform and allyl alcohol binary mixture

The objective of this study was to evaluate the interaction profile of chloroform (CHCl3)+allyl alcohol (AA) binary mixture (BM)-induced acute hepatotoxic response. Plasma alanine amino transferase (ALT) was measured to assess liver injury, and H-3-thymidine (H-3-T) incorporation into hepatonuclear DNA was measured as an index of liver regeneration over a time course of 0-72 h. Male Sprague-Dawley (S-D) rats received single ip injection of 5-fold dose range of CHCl3 (74, 185 and 370 mg/kg) in corn oil (maximum 0.5 ml/kg) and 7-fold dose range of AA (5, 20 and 35 mg/kg) in distilled water simultaneously. The doses for BM were selected from individual toxicity studies of CHCl3 alone [Int. J. Toxicol. 22 (2003) 25], and AA alone [Reg. Pharmacol. Toxicol. 19 (1999) 165]. Since the highest dose of each treatment (CHCl3- 740 and AA- 50 mg/kg) yielded mortality due to the suppressed tissue repair followed by liver failure, this dose was omitted for BM. The levels of CHCl3 (30-360 min) and AA (5-60 min) were quantified in blood and liver by gas chromatography (GC). The liver injury was more than additive after BM compared to CHCl3 alone or AA alone at highest dose combination (370 + 35 mg/kg), which peaked at 24 h. The augmented liver injury observed with BM was consistent with the quantitation data. Though the liver injury was higher, the greater stimulation of tissue repair kept injury from progressing, and rescued the rats from hepatic failure and death. At lower dose combinations, the liver injury was no more than additive. Results of the present study suggest that liver tissue repair, in which liver tissue lost to injury is promptly replaced, plays a pivotal role in the final outcome of liver injury after exposure to BM of CHCl3 and AA. (C) 2003 Elsevier Science Ltd. All rights reserved.