Evaluation of sex difference in tissue repair following acute carbon tetrachloride toxicity in male and female Sprague-Dawley rats

Cellular regeneration and tissue repair greatly influence the outcome of ac ute carbon tetrachloride (CCl4) hepatotoxicity. This study examined the tem poral kinetics of cellular regeneration and tissue repair processes in male and female Sprague-Dawley (SD) rats following an acute CCl4, exposure (0.8 ml/kg, i.p.). In female rats, hepatic damage peaked at 24 h following the treatment and was similar to 2.5-fold (AST 2.7-fold, ALT 2.3 fold) greater than the damage observed in male rats. The hepatic damage in male rats appe ared to peak by 3 h post-exposure and did not significantly change through the 36-h time-point. The activity of cytochrome P 4502E1 was 20% greater in male rats and did not correlate with the magnitude of hepatic damage. Morp hometric analysis of cell cycle indices revealed that cellular regeneration was significantly greater in female rats as compared to male rats at 48 h and corresponded proportionally to the extent of liver damage. This study d emonstrated that female SD rats respond more severely to acute CCl4, hepato toxicity than male SD rats and the extent of tissue repair and cellular reg eneration was greater in female rats. Furthermore, our results suggest that tissue repair is unlikely to result in accounting for the different respon ses exhibited by male and female SD rats to CCl4, hepatotoxicity. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.