Ethanol modulates gut ischemia/reperfusion-induced liver injury in rats

Abstract

Whereas both ethanol and gut ischemia/reperfusion (I/R) are known to alter hepatic microvascular function, little is known about the influence of ethanol consumption on the hepatic microvascular responses to I/R. The objective of this study was to determine whether acute ethanol administration exacerbates the hepatic microvascular dysfunction induced by gut I/R. Rats were exposed to gut ischemia for 30 min followed by reperfusion. Intravital videomicroscopy was used to monitor leukocyte recruitment and the number of nonperfused sinusoids (NPS). Plasma alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and endotoxin concentrations were monitored. In separate experiments, ethanol was administered 15 min or 24 h before gut ischemia. In control rats, gut I/R increased the number of stationary leukocytes and NPS. It also elevated the plasma ALT, TNF-α, and endotoxin with a corresponding increase in intestinal mucosal permeability. Low-dose ethanol consumption 15 min before gut ischemia blunted the gut I/R-induced leukostasis and elevations in plasma TNF-α and ALT. However, high-dose ethanol consumption aggravated the gut I/R-induced increases in leukostasis and increases in plasma endotoxin and ALT. When ethanol was administered 24 h before, high-dose ethanol aggravated the gut I/R-induced hepatocellular injury, but low-dose ethanol did not have any effects on it. These results suggest that low-dose ethanol consumption shortly before gut ischemia attenuates the hepatic inflammatory responses, microvascular dysfunction, and hepatocellular injury elicited by gut I/R, whereas high-dose ethanol consumption appears to significantly aggravate these gut I/R-induced responses.

The role of hypoxia in the pathogenesis of alcoholic liver disease

“…For instance, rats undergoing gut ischemia/reperfusion (I/R) liver injury respond to high and low dose ethanol differently. Rats fed low dose ethanol (1 g) plus I/R showed a reduction in the percentage of non-perfused sinusoids in the liver as visualized by intravital microscopy, whereas, rats fed high dose ethanol plus I/R showed an increase in the percentage of non-perfused sinusoids [43]. This beneficial effect of low dose ethanol on I/F was partially inhibited by l-NMMA [44] indicating that nitric oxide was involved in decreasing non-perfused sinusoids in the I/F injured livers.…”

Oxymatrine attenuates intestinal ischemia/reperfusion injury in rats

“…1 During I/R, tissues are subjected to the destructive proinfl ammatory cytokines and reactive oxygen species released by infl ammatory cells, leading to infl ammatory injury and cell apoptosis. 2,3 Intestinal I/R can also cause injury to the secondary organs [4][5][6][7] and even multiple organ failure (MOF). Therefore, novel agents to attenuate intestinal I/R are being sought urgently.…”

Taurine Attenuates Multiple Organ Injury Induced by Intestinal Ischemia Reperfusion in Rats

“…During ischemia reperfusion (I/R), tissues are subjected to the destructive proinflammatory cytokines and reactive oxygen species released by inflammatory cells, leading to inflammatory injury and cell apoptosis [2,3]. II/R also affects the secondary organs, including liver [4], heart [5], kidney [6], and lung [7], and even causes multiple organ failure (MOF), a common cause of mortality. Therefore, seeking anti-oxidative, anti-inflammatory, and antiapoptotic agents to attenuate multiple organ injury induced by II/R is urgently required.…”