Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats.
This study investigated the time course of heme oxygenase (HO)-1 expression and the role of endogenous HO-1 in hepatic ischemia and reperfusion (I/R). Rats were pretreated with hemin, an HO-1 inducer, and zinc protoporphyrin (ZnPP), an HO-1 inhibitor. Hepatic HO activity increased at 1 h after reperfusion, reaching a maximum at 6 h after reperfusion and then declined. HO-1 mRNA and protein expression in I/R liver were upregulated prior to reperfusion and highly induced again by reperfusion. The ALT level was upregulated at all time points, with a peak at 4-6 h. This increase was augmented by ZnPP but attenuated by hemin. Lipid peroxidation and serum HMGB1 release significantly increased at 1 h after reperfusion and remained elevated throughout the 24 h of reperfusion period, whereas the glutathione content decreased markedly at 4-6 h after reperfusion. These changes were attenuated by hemin but augmented by ZnPP. The levels of serum TNF-α, iNOS, and COX-2 protein and mRNA expressions were upregulated after reperfusion, further enhanced by ZnPP, and suppressed by hemin. HO-1 overexpression protects the liver against I/R injury by modulating oxidative stress and proinflammatory mediators.
Yun
Nari
N
School of Pharmacy, Sungkyunkwan University , Suwon-si, South Korea .
Eum
Hyun-Ae
HA
Lee
Sun-Mee
SM
D000818:Animals; D024243:HMGB1 Protein / Q000097:blood; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000008:administration & dosage; D015227:Lipid Peroxidation; D008107:Liver Diseases / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D011524:Protoporphyrins / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D011524:Protoporphyrins; D012333:RNA, Messenger; C017803:zinc protoporphyrin; D006427:Hemin; D051547:Heme Oxygenase-1