Conflicts of interest: The authors declare no conflict of interest.
Protective effect of heme oxygenase-1 on hepatic ischemia-reperfusion injury through inhibition of platelet adhesion to the sinusoids
Version of Record online: 25 MAR 2013
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 4, pages 700–706, April 2013
How to Cite
Tamura, T., Kondo, T., Ogawa, K., Fukunaga, K. and Ohkohchi, N. (2013), Protective effect of heme oxygenase-1 on hepatic ischemia-reperfusion injury through inhibition of platelet adhesion to the sinusoids. Journal of Gastroenterology and Hepatology, 28: 700–706. doi: 10.1111/jgh.12075
- Issue online: 25 MAR 2013
- Version of Record online: 25 MAR 2013
- Accepted manuscript online: 6 DEC 2012 08:37AM EST
- Manuscript Accepted: 29 OCT 2012
- carbon monoxide;
- intravital microscopy;
- Kupffer cell;
Background and Aim
Heme oxygenase-1 (HO-1) acts as a protector against hepatic inflammatory injury. HO-1 catalyzes the conversion of heme protein to biliverdin, free iron, and carbon monoxide. Pro-inflammatory responses play critical roles in hepatic ischemia-reperfusion (I/R) injury, and carbon monoxide effectively downregulates I/R injury. The aim of this study was to evaluate the mechanism by which HO-1 reduces warm I/R injury.
Sprague–Dawley rats were divided into two groups: the 20-min ischemia group (control group; n = 6) and the 20-min ischemia with cobalt protoporphyrin (CoPP group; n = 6). CoPP is an inducer of HO-1 in the sinusoids. Kupffer cells were labeled using the liposome entrapment method, and platelets were labeled with rhodamine-6G. The adherent platelets were observed for up to 120 min after reperfusion by intravital microscopy.
In the control group, the number of adherent platelets significantly increased than in the CoPP group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were observed after 120 min of reperfusion in the control group. They were not observed in the CoPP group. In the CoPP group, serum alanine transaminase and interleukin-6 levels reduced after reperfusion. Moreover, the flow velocity of platelets in the hepatic sinusoid markedly increased.
This study suggests that HO-1 inhibits platelet adhesion to sinusoids. Such inhibition leads to the prevention of hepatic I/R injury.