Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 309, Issue 4, Pages 857-863Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2003.08.085
Keywords
acetaminophen; hepatotoxicity; interleukin 6; regeneration; cytokines; proliferating cell nuclear antigen; glutathione; murine macrophage inhibitory protein-2; monocyte chemoattractant protein-1; tumor necrosis factor-alpha
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Funding
- NIDDK NIH HHS [DK 02971] Funding Source: Medline
- NIGMS NIH HHS [GM 58884] Funding Source: Medline
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To determine the importance of IL-6 in acetaminophen (APAP) toxicity, wild type (WT) and IL-6 knock out (KO) mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 4 and 24 h. No differences were found between the two groups by analysis of serum AST levels or histopathology. Also, the relative amounts of APAP protein binding and nitrotyrosine formation were equal. Subsequently, WT and KO mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 24, 48, and 72 h. AST normalized by 48 h in the WT mice, but not until 72h in the KO mice. The severity of the histopathological alterations was comparable in the two groups of mice; however, fewer regenerating hepatocytes were present in the KO mice. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed reduced staining in the KO mice. Pretreatment of KO mice with IL-6 lowered AST and normalized PCNA staining in the IL-6 KO mice. These data suggest that IL-6 is important in hepatocyte regeneration following APAP toxicity in the mouse. (C) 2003 Elsevier Inc. All rights reserved.
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