Antibiotics prevent liver injury in rats following long-term exposure to ethanol

doi:10.1016/0016-5085(95)90027-6

Gastroenterology

Volume 108, Issue 1, January 1995, Pages 218-224

https://doi.org/10.1016/0016-5085(95)90027-6 Get rights and content

Abstract

$Background/Aims:$ Kupffer's cells participate in alcohol-induced liver injury, and endotoxemia is observed in human alcoholics and in a rat model. This study evaluated the effect of reducing bacterial endotoxin production by intestinal sterilization on alcohol-induced liver injury. $Methods:$ Male Wistar rats were exposed to ethanol continuously for up to 3 weeks via intragastric feeding. The gut was sterilized with polymyxin B and neomycin. $Results:$ Fecal culture of stool samples from ethanol-fed rats treated with antibiotics showed virtually no growth of gram-negative bacteria. Endotoxin levels of 80–90 pg/mL in plasma of ethanol-fed rats were reduced to <25 pg/mL by antibiotics. Antibiotic treatment also completely prevented elevated aspartate aminotransferase levels and significantly reduced the average hepatic pathological score in rats exposed to ethanol. Oxygen tension on the surface of the liver measured in vivo was decreased significantly from control values of 48 ± 1 to 39 ± 1 μmol/L in ethanol-treated rats. This hypoxia was prevented by treatment with antibiotics. Moreover, the increase in rates of ethanol elimination due to long-term ethanol treatment was prevented by antibiotic treatment. $Conclusions:$ Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.

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^☆: Supported in part by grants AA-03624 and AA-09156 from the National Institute on Alcohol Abuse and Alcoholism. Y.A. was supported in part by a fellowship from the American Liver Foundation.

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Antibiotics prevent liver injury in rats following long-term exposure to ethanol☆

Abstract

J Surg Res

J Hepatol

Hepatology

Gastroenterology

Biochem Pharmacol

Lancet

Lancet

J Surg Res

Med Clin North Am

Liver damage in chronic alcoholism

Long-term cannulation model for blood sampling and intragastric infusion in the rat

Am J Physiol

Ethanol-induced hepatic fibrosis in the rat: role of the amount of dietary fat

Alcohol Clin Exp Res

Inactivation of Kupffer cells prevents early alcohol-induced liver injury

Hepatology

Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation

J Leukoc Biol

Mechanisms of alcohol-induced liver injury: hypoxia and role of Kupffer cells

Toxicologist

Kupffer cells are required for the swift increase in alcohol metabolism

Res Commun Subst Abuse

Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis

Res Exp Med