Role of ICAM-1 in chronic ethanol consumption-enhanced liver injury after gut ischemia-reperfusion in rats.
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| Abstract |
Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the hepatic microvascular dysfunction elicited by gut ischemia-reperfusion (I/R). Although the effects of chronic ethanol (EtOH) consumption on the liver are well known, it remains unclear whether this condition renders the hepatic microcirculation more vulnerable to the deleterious effects of gut and/or hepatic I/R. The objectives of this study were to determine whether chronic EtOH consumption alters the severity of gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury and to determine whether ICAM-1 contributes to this response. Male Wistar rats, pair fed for 6 wk a liquid diet containing EtOH or an isocaloric control diet, were exposed to gut I/R. Intravital video microscopy was used to monitor leukocyte recruitment in the hepatic microcirculation, the number of nonperfused sinusoids (NPS), and plasma concentrations of endotoxin and tumor necrosis factor-alpha. Plasma alanine aminotransferase (ALT) levels were measured 6 h after the onset of reperfusion. In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma endotoxin, tumor necrosis factor-alpha, and ALT. In EtOH-fed rats, the gut I/R-induced increases in NPS and leukostasis were blunted in the midzonal region, while exaggerated leukostasis was noted in the pericentral region and terminal hepatic venules. Chronic EtOH consumption also enhanced the gut I/R-induced increase in plasma endotoxin and ALT. The exaggerated responses to gut I/R normally seen in EtOH-fed rats were largely prevented by pretreatment with a blocking anti-ICAM-1 monoclonal antibody. In conclusion, these results suggest that chronic EtOH consumption enhances gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury in the pericentral region and terminal hepatic venules via an enhanced hepatic expression of ICAM-1.
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| Authors | Yoshinori Horie, Yoshiyuki Yamagishi, Shinzo Kato, Mikio Kajihara, Hironao Tamai, D Neil Granger, Hiromasa Ishii |
| Journal | American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 283 Issue 3 Pg. G537-43 (Sep 2002) ISSN: 0193-1857 [Print] United States |
| PMID | 12181165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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