Role of flavin-containing-monooxygenase-dependent neutrophil activation in thioacetamide-induced hepatic inflammation in rats

Dur Zong Hsu, Pei Yi Chu, Ya Hui Li, Victor Raj Mohan Chandrasekaran, Ming Yie Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Thioacetamide is widely used in industry and is known to be one of the most potent hepatotoxicants in experimental animals. We investigated the involvement of flavin-containing monooxygenase (FMO)-dependent hepatic-neutrophil activation and the release of proinflammatory mediators in thioacetamide-induced hepatic injury in rats. Thioacetamide (100. mg/kg, intraperitoneally) increased, within 12. h, hepatic serum aspartate transferase and alanine transferase levels, tumor necrosis factor-α production, interleukin-1β and nitrite levels, and myeloperoxidase activity. Rabbit anti-neutrophil serum markedly inhibited all thioacetamide-altered parameters. In addition, FMO-competitive inhibitor methimazole reduced thioacetamide-induced myeloperoxidase activity, hepatic tumor necrosis factor-α, interleukin-1β, nitrite, inducible nitric oxide synthase, and hepatic damage in thioacetamide-treated rats. Thus, we conclude that FMO-dependent hepatic neutrophil activation initiates the release of proinflammatory mediators in thioacetamide-treated rats.

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalToxicology
Volume298
Issue number1-3
DOIs
Publication statusPublished - 2012 Aug 16

All Science Journal Classification (ASJC) codes

  • Toxicology

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