Protective effect of heme oxygenase-1 on hepatic ischemia-reperfusion injury through inhibition of platelet adhesion to the sinusoids.

Abstract

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

This study suggests that HO-1 inhibits platelet adhesion to sinusoids. Such inhibition leads to the prevention of hepatic I/R injury.

• Authors: Takafumi Tamura, Tadashi Kondo, Koichi Ogawa, Kiyoshi Fukunaga, Nobuhiro Ohkohchi
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 28 Issue 4 Pg. 700-6 (Apr 2013) ISSN: 1440-1746 [Electronic] Australia
• PMID: 23215739 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Chemical References

• Interleukin-6
• Protoporphyrins
• cobaltiprotoporphyrin
• Heme Oxygenase-1
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Blotting, Western
• Disease Models, Animal
• Heme Oxygenase-1 (physiology)
• Interleukin-6 (metabolism)
• Kupffer Cells (metabolism)
• Liver (enzymology, metabolism)
• Liver Diseases (enzymology, physiopathology, prevention & control)
• Male
• Platelet Adhesiveness (physiology)
• Postoperative Complications
• Protoporphyrins (toxicity)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (chemically induced, enzymology, prevention & control)