Hepatic Microvascular Dysfunction in Endotoxemic Rats After Acute Ethanol Administration

Horie, Yoshinori; Kato, Shinichi; Ohki, Eiji; Tamai, Hironao; Yamagishi, Yuka; Ishii, Hiromasa

doi:10.1097/00000374-200005000-00014

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…The latter observations are consistent with other reports demonstrating that bacterial endotoxin can induce hepatic microvascular dysfunction and liver injury (11). Furthermore, in endotoxemic animals, even relatively low-dose ethanol that cannot cause hepatic microvascular dysfunction alone induced hepatic microvascular dysfunction (12). Thus interaction between ethanol and endotoxin on hepatic microcirculation has been recognized.…”

supporting

confidence: 91%

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

Yamagishi

Horie

Kato

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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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.

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confidence: 91%

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

Yamagishi

Horie

Kato

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…LPS plays a major role in the alcohol-induced liver inflammation and the pathogenesis of ALD [12, 13]. Furthermore, LPS enhances ethanol-induced hepatic microvascular dysfunction, liver injury and apoptosis [14, 15, 16]. Acute and chronic alcohol intake increases portal and systemic LPS in patients and animal models of ALD and has a positive correlation with the severity of the disease [13,17].…”

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confidence: 99%

Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice

et al. 2017

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Backgrounds & Aims Bacterially-derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease. Methods Mice underwent acute binge or chronic ethanol exposure to induce alcoholic liver injury and steatosis +/− IAP supplementation. Liver tissue was assessed for biochemical, inflammatory and histopathological changes. An ex vivo co-culture system was used to examine the effects of alcohol and IAP treatment in regard to the activation of hepatic stellate cells and their role in the development of alcoholic liver disease. Results Pretreatment with IAP resulted in significantly lower serum alanine aminotransferase (ALT) compared to the ethanol alone group in the acute binge model. IAP treatment attenuated the development of alcohol-induced fatty liver, lowered hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol-induced gut barrier dysfunction. Finally, IAP ameliorated the activation of hepatic stellate cells and prevented their lipogenic effect on hepatocytes. Conclusions IAP treatment protected mice from alcohol-induced hepatotoxicity and steatosis. Oral IAP supplementation could represent a novel therapy to prevent alcoholic-related liver disease in humans.

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“…[1][2][3][4][5] The structural and functional alterations of sinusoidal endothelial fenestrae also have been reported to involve impaired microcirculatory exchange of fluids and solutes between the sinusoidal lumen and the space of Disse. 6,7 In experimental and human studies, plasma hyaluronic acid levels are elevated in alcoholic liver injury, which may reflect a diminished hepatic clearance in SECs.…”

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Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: Role of intracellular calcium and nitric oxide

et al. 2006

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In alcoholic liver disease, ethanol-induced damage to sinusoidal endothelial cells (SECs) appears to be important in the progression of liver damage. However, little is known about the mechanisms responsible for protection of SECs against ethanol-induced injury. To elucidate the role of sphingosine 1-phosphate (S1P), which is stored in platelets and may be released from them on their activation, we investigated the effect of S1P on rat liver SECs in primary culture. Pretreatment of cells with 1 mol/L S1P attenuated ethanol-induced apoptosis. Electron microscopy confirmed this protective effect of S1P on damaged SECs in liver tissues after perfusion of ethanol. In the absence of ethanol, S1P increased DNA synthesis as determined via incorporation of bromodeoxyuridine. S1P also ameliorated the decreased DNA synthesis of cells induced by ethanol. Addition of S1P to cells induced an increase in intracellular calcium concentrations and NO production in cells. Western blotting revealed that S1P significantly induced the activation of endothelial NO synthase (eNOS), but not Akt, and that S1P-induced activation of eNOS was blocked by trifluoperazine, a calmodulin inhibitor. Furthermore, N G -nitro-L-arginine methyl ester, a NO synthase inhibitor, cancelled the effect of S1P on DNA synthesis, apoptosis, and NO production in vitro as well as the protective effect of S1P on cell damage in situ. In conclusion, the biological effect of S1P is at least partially mediated by Ca 2؉ -sensitive eNOS activation and subsequent NO formation; extracellular S1P could contribute to sinusoidal protection and remodeling in alcoholic liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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Hepatic Microvascular Dysfunction in Endotoxemic Rats After Acute Ethanol Administration

Abstract: These results suggest that LPS synergistically enhances ethanol-induced hepatic microvascular dysfunction and liver injury, especially in the midzonal region via coagulation, which may be mediated by TNF-alpha.

Cited by 11 publications

References 27 publications

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

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

Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice

Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: Role of intracellular calcium and nitric oxide

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