Gene expression on liver toxicity induced by administration of haloperidol in rats with severe fatty liver
Gene expression on liver toxicity induced by administration of haloperidol in rats with severe fatty liver
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DOI：
10.1016/j.legalmed.2007.12.006
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发表时间：
2008-07-01
期刊：
影响因子：
1.5
通讯作者：
Nata, Masayuki
中科院分区：
文献类型：
--
作者：
Hanagama, Masakazu;Inoue, Hiromasa;Nata, Masayuki
在服用抗精神病药物的精神分裂症患者中经常会遇到猝死，脂肪肝在精神分裂症患者中可能更普遍。本研究旨在探讨抗精神病药物对脂肪肝的不良影响。我们给氟哌啶醇腹腔注射脂肪肝大鼠，并检查在肝脏中的mRNA表达。脂肪肝中细胞色素P450（CYP）1A2、CYP2C11和CYP3A2的基础表达降低，这些CYP对氟哌啶醇的反应性降低。氟哌啶醇在脂肪肝大鼠中的代谢也受到抑制。此外，在严重脂肪肝中，病理组织学和分子生物学显示了氟哌啶醇给药引起的肝损伤。这些结果表明，脂肪肝增加了对氟哌啶醇不良反应的易感性，可能导致危及生命的事件。临床医生应注意，过量服用抗精神病药物对脂肪肝患者的危害可能更大。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Sudden deaths are often encountered in schizophrenic patients prescribed with antipsychotic drugs, and fatty liver may be more prevalent among patients with schizophrenia. The aim of this study is to investigate the adverse effects of antipsychotic drugs on fatty liver. We administered haloperidol intraperitoneally to fatty liver rats and examined the mRNA expression in the liver. Basic expressions of cytochrome P450 (CYP)1A2, CYP2C11 and CYP3A2 decreased, and response of these CYPs to haloperidol was reduced in the fatty liver. Metabolism of haloperidol was also suppressed in the fatty liver rats. Moreover, hepatic injury by administration of haloperidol was shown pathohistologically and molecular-biologically in severe fatty liver. These results suggest that fatty liver increases susceptibility to adverse effects of haloperidol, possibly leading to life-threatening events. It should be noted by clinicians that excessive dose of antipsychotic drugs may be more harmful in patients with fatty liver. (C) 2008 Elsevier Ireland Ltd. All rights reserved.