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• W2151875144 endingPage "215" @default.
• W2151875144 startingPage "208" @default.
• W2151875144 abstract "Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants including aflatoxin B(1) (AFB(1)). Mediators of inflammation, in particular neutrophils (PMNs), are responsible for tissue injury in a variety of animal models. This study was conducted to examine the role of PMNs in the pathogenesis of hepatic injury after AFB(1)/LPS cotreatment. Male, Sprague-Dawley rats (250-350 g) were treated with either 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 10(6) EU/kg, iv) or its saline vehicle. Over a course of 6 to 96 h after AFB(1) administration, rats were killed and livers were stained immunohistochemically for PMNs. LPS resulted in an increase in PMN accumulation in the liver that preceded the onset of liver injury. To assess if PMNs contributed to the pathogenesis, an anti-PMN antibody was administered to reduce PMN numbers in blood and liver, and injury was evaluated. 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. Neutrophil depletion protected against hepatic parenchymal cell injury caused by AFB(1)/LPS cotreatment but not against markers of biliary tract injury. This suggests that LPS augments AFB(1) hepatotoxicity through two mechanisms: one of which is PMN-dependent, and another that is not." @default.
• W2151875144 created "2016-06-24" @default.
• W2151875144 creator A5001438738 @default.
• W2151875144 creator A5028376473 @default.
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• W2151875144 date "2000-11-01" @default.
• W2151875144 modified "2023-09-23" @default.
• W2151875144 title "Lipopolysaccharide Augments Aflatoxin B1-Induced Liver Injury through Neutrophil-Dependent and -Independent Mechanisms" @default.
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• W2151875144 doi "https://doi.org/10.1093/toxsci/58.1.208" @default.
• W2151875144 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11053557" @default.
• W2151875144 hasPublicationYear "2000" @default.
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