Ap. Moghaddam et al., Evaluation of sex difference in tissue repair following acute carbon tetrachloride toxicity in male and female Sprague-Dawley rats, TOXICOLOGY, 130(2-3), 1998, pp. 95-105
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.