Heme oxygenase-1 induction by hemin protects liver cells from ischemia/reperfusion injury in cirrhotic rats.
OBJECTIVE
To investigate the potential protective effect of HO-1 on cirrhotic liver cells in rats.


METHODS
Male Wistar rats included in the current study were randomly divided into 5 groups as follows: normal (N) group; liver cirrhotic (LC) group; sham (S) group; I/R group and I/R + hemin group. The model for inducing liver cirrhosis in rats was established according to a previously published protocol. Following this the segmental hepatic ischemia reperfusion operation was carried out. The rats were treated with 30 micromol/kg hemin (HO-1 inducer, ferric portoporphyrin IX chloride) i.p. or 0.9% NaCl (control) 24 h and 12 h before hepatic ischemia for 30 min or sham laparotomy. Blood was collected for serum enzymatic measurement 6 and 12 h after reperfusion or sham laparotomy. HO-1, NF-kappaB and caspase-3 expressions were assessed by immunohistochemical analysis.


RESULTS
The expressions of proteins are inversely correlated to the gray values. HO-1 expression in the I/R + hemin group was increased significantly than I/R group at 6 h and 12 h after hepatic I/R (6 h: 112.0 +/- 8.3 vs 125.1 +/- 5.7, P < 0.01; 12 h: 120.8 +/- 11.0 vs 132.4 +/- 6.2, P < 0.01). Hemin improved serum manganese superoxide dismutase (MnSOD) (6 h: 131.3 +/- 17.6 vs 107.0 +/- 13.9, P < 0.01; 12 h: 141.4 +/- 12.5 vs 118.3 +/- 10.2, P < 0.01), lessened liver cell injury, decreased caspase-3(6 h: 166.7 +/- 8.1 vs 145.5 +/- 14.6, P < 0.01; 12 h: 172.8 +/- 3.8 vs 148.0 +/- 6.5, P < 0.01) and NF-kappaB expression (6 h: 150.2 +/- 8.6 vs 139.7 +/- 6.0, P < 0.01; 12 h: 151.1 +/- 5.9 vs 148.1 +/- 5.3, P > 0.05) and serum alanine aminotransferase (ALT) (6 h: 413.3 +/- 104.1 vs 626.8 +/- 208.2, P < 0.01; 12 h: 322.2 +/- 98.8 vs 425.8 +/- 115.4, P < 0.05), aspartate aminotransferase (AST) (6 h: 665.2 +/- 70.1 vs 864.3 +/- 70.4, P < 0.01; 12 h: 531.1 +/- 98.6 vs 664.4 +/- 115.6, P < 0.01), malondialdehyde (MDA) levels (6 h: 11.1 +/- 2.17 vs 13.5 +/- 2.01, P < 0.01; 12 h: 9.36 +/- 1.10 vs 10.8 +/- 1.62, P < 0.05) in the I/R + hemin group when compared with the I/R group.


CONCLUSIONS
These results suggest that HO-1 plays an important role in protecting liver cells from hepatic I/R injury in cirrhotic rats by decreasing oxidative stress, apoptosis and inflammation.
Xue
Hui
H
Department of Gastroenterology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China. zj2@mail.xjtu.edu.cn
Guo
Hua
H
Li
Ying-Chao
YC
Hao
Zhi-Ming
ZM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
D016328:NF-kappa B; D006427:Hemin; D002251:Carbon Tetrachloride; D051547:Heme Oxygenase-1; D053148:Caspase 3