Abstract
Heme oxygenase (HO)-1 has been shown to be beneficial in a variety of ischemia/reperfusion (I/R) models. However, there are no studies examining the relationship between the upregulation of HO-1 expression and the development of I/R injury in the reperfused liver. Therefore, the purpose of this study was to determine the protective role of upregulated HO-1 expression during hepatic I/R. Rats were subjected to 60 min of hepatic ischemia, liver and blood samples were taken 0, 1, 2, 4, 6, 8, 12 and 24 hr after reperfusion. HO activity in the liver increased significantly at 1 hr after reperfusion and reached maximum at 6 hr after reperfusion, and then declined gradually. Rats were pretreated twice with ZnPP (6.74 mg/kg, an inhibitor of HO activity) or with hemin (30 mg/kg, an inducer of HO expression and activity) at 16 and 3 hr prior to ischemia. The serum ALT level increased markedly immediately following reperfusion and peaked between 4 and 6 hr and then declined gradually. This increase was significantly augmented by ZnPP but was attenuated by hemin. iNOS protein and iNOS mRNA were upregulated markedly at 4 hr after reperfusion, which was suppressed by hemin. Conversely, in the ZnPP-treated group, the iNOS induction resulting from I/R was markedly enhanced. Immediately after reperfusion, the COX-2 mRNA significantly increased in I/R group and this increase remained until at 6 hr after reperfusion. The increase in the COX-2 mRNA expression was potentiated by ZnPP but attenuated by hemin at all time points. In the rats pretreated with ZnPP and subjected to hepatic I/R, the plasma TNF-α content and its mRNA level were significantly higher than that observed in the serum of control rats subjected to I/R. However, the TNF-α content in rats pretreated with hemin and subjected to I/R was attenuated. Consequently, prior induction of HO-1 expression may provide a new strategy to protect livers against injury caused by ischemia/reperfusion which occur in liver transplantation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
