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 acute carbon tetrachloride (CCl4) hepatotoxicity. This study examined the temporal 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 approximately 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 appeared 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. Morphometric 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 demonstrated that female SD rats respond more severely to acute CCl4 hepatotoxicity than male SD rats and the extent of tissue repair and cellular regeneration was greater in female rats. Furthermore, our results suggest that tissue repair is unlikely to result in accounting for the different responses exhibited by male and female SD rats to CCl4 hepatotoxicity.
Moghaddam
A P
AP
Operational Toxicology Branch, Air Force Research Laboratory, Wright-Patterson AFB, OH 84056-5012, USA. moghadda@hillwpos.hill.af.mil
Eggers
J S
JS
Calabrese
E J
EJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D009336:Necrosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D018809:Proliferating Cell Nuclear Antigen; D014280:Triglycerides; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase