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Title: Bacterial lipopolysaccharide exposure augments aflatoxin B(1)-induced liver injury.

Authors: Barton, C C; Hill, D A; Yee, S B; Barton, E X; Ganey, P E; Roth, R A

Published In Toxicol Sci, (2000 Jun)

Abstract: Bacterial endotoxin (lipopolysaccharide; LPS) given to animals in large doses results in pronounced, midzonal liver injury. Exposure to smaller, non-injurious doses of LPS augments the toxicity of certain hepatotoxicants. This study was conducted to delineate the development of injury in a rat model of augmentation of aflatoxin B(1) (AFB(1)) hepatotoxicity by LPS. At large doses (i.e., > 1 mg/kg, ip), AFB(1) administration resulted in pronounced injury to the periportal regions of the liver. Male, Sprague-Dawley rats (250-350 g) were treated with 1 mg AFB(1)/kg, ip or its vehicle (0.5% DMSO/saline) and 4 h later with either E. coli LPS (7.4 x 106 EU/kg, iv) or its saline vehicle. Liver injury was assessed 6, 12, 24, 48, 72, or 96 h after AFB(1) administration. Hepatic parenchymal cell injury was evaluated as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and from histologic examination of liver sections. Biliary tract alterations were evaluated as increased concentration of serum bile acids and activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5'-ND) in serum. At all times and for all markers, injury in rats treated with either AFB(1) or LPS alone was absent or modest. In the AFB(1)/LPS cotreated group, hepatic parenchymal cell injury was pronounced by 24 h and had returned to control values by 72 h. The injury began in the periportal region and spread midzonally with time. Furthermore, changes in serum markers indicative of biliary tract alterations were evident by 12 h and had returned to control values by 72 h. Thus, the nature of the hepatic lesions suggested that LPS potentiated the effects of AFB(1) on both parenchymal and bile duct epithelial cells.

PubMed ID: 10828277 Exiting the NIEHS site

MeSH Terms: 5'-Nucleotidase/blood; Aflatoxin B1/pharmacology*; Alanine Transaminase/blood; Alkaline Phosphatase/blood; Animals; Apoptosis/drug effects; Aspartate Aminotransferases/blood; Bile Acids and Salts/blood; Chemical and Drug Induced Liver Injury/blood; Chemical and Drug Induced Liver Injury/etiology*; Chemical and Drug Induced Liver Injury/pathology; Cholestasis/blood; Cholestasis/chemically induced; Cholestasis/pathology; Drug Synergism; Escherichia coli; In Situ Nick-End Labeling; Lipopolysaccharides/pharmacology*; Liver/drug effects*; Liver/pathology; Male; Rats; Rats, Sprague-Dawley; gamma-Glutamyltransferase/blood

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