Dynamic changes of heme oxygenase-1 and carbon monoxide production in acute liver injury induced by carbon tetrachloride in rats.
Heme oxygenase-1, a stress-responsive enzyme that catabolizes hemes into carbon monoxide, biliverdin, and iron, has been shown to play a pivotal role in many physiological and pathological situations. Here we investigated changes in HO-1 enzyme activity and protein expression, and its end product carbon monoxide concentrations in the liver of rats after CCl(4) treatment. We found that CCl(4) administration not only induced severe liver damage in rats, as demonstrated by dramatic elevation of ALT, AST levels and severe histopathological changes, but also resulted in a prominent up-regulation of HO-1 enzyme activity. Western blot and immunohistochemical analysis confirmed that expression of HO-1 protein was also increased significantly in a time-dependent manner following CCl(4) treatment, and localized mainly in liver cells around the central vein. In addition, CO concentrations in the liver of CCl(4)-treated rats were elevated remarkably in the same time-dependent way as HO-1 induction in contrast to the control rats. These data indicated that HO-1/CO pathway was greatly up regulated in the liver of rats after CCl(4) treatment, which might play an important protective role in the pathophysiological mechanism underlying CCl(4)-induced hepatotoxicity. It therefore suggested that more relevant studies should be carried out in the future to clarify the detailed mechanisms.
Wen
Tao
T
Research Center of Occupational Medicine, The Third Hospital of Peking University, Beijing, PR China.
Guan
Li
L
Zhang
Yan-Lin
YL
Zhao
Jin-Yuan
JY
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D002248:Carbon Monoxide; D002251:Carbon Tetrachloride; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase