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

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• 作者：Dur-Zong Hsu^a ; ^{durzonghsu@gmail.com} ; Pei-Yi Chu^a ; Ya-Hui Li^a ; Victor Raj Mohan Chandrasekaran^a ; Ming-Yie Liu^a ; ^b ; ^{myliu@mail.ncku.edu.tw}
• 关键词：Thioacetamide ; Proinflammatory mediators ; Neutrophil infiltration ; Flavin-containing-monooxygenase ; Hepatic injury ; Rats
• 刊名：Toxicology
• 出版年：2012
• 期刊代码：47_0300483x
• 类别：pha
• 出版时间：16 August, 2012
• 卷：298
• 期：1-3
• 页码：52-58
• 文件大小：958 K

摘要

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-伪 production, interleukin-1尾 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-伪, interleukin-1尾, 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.