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伯氏疟原虫(ANKA株):感染可诱导小鼠肝脏中的CYP2A5和2E1,同时抑制其他CYP同工酶。

Plasmodium berghei (ANKA): infection induces CYP2A5 and 2E1 while depressing other CYP isoforms in the mouse liver.

作者信息

De-Oliveira Ana C A X, Da-Matta Anndressa C, Paumgartten Francisco J R

机构信息

Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.

出版信息

Exp Parasitol. 2006 Aug;113(4):256-61. doi: 10.1016/j.exppara.2006.01.013. Epub 2006 Mar 15.

Abstract

It has been reported that malaria infection impairs hepatic drug clearance and causes a down-regulation of CYP-mediated monooxygenase activities in rodents and humans. In the present study, we investigated the effects of Plasmodium berghei infection on the activity of liver monooxygenases in female DBA/2 and C57BL/6 mice. In both mouse strains, P. berghei infection decreased activities mediated by CYP1A (EROD: DBA/2 65.3%, C57BL/6 44.7%) and 2B (BROD: DBA/2 64.3%, C57BL/6 49.8%) subfamily isoforms and increased activities mediated by 2A5 (COH: DBA/2 182.4%, C57BL/6 148.5%) and 2E1 (PNPH: DBA/2 177.8%, C57BL/6 128.5%) isoforms as compared to non-infected controls. Since malaria infection also produced an increase in ALT (273.1%) and AST (354.1%) activities in the blood serum, our findings are consistent with the view that CYP2A5 activity is induced by liver injury. An almost generalized depression of CYP-mediated activities has been found with numerous infections and inflammatory stimuli but an induction of CYP2A5 had been previously noted only in some viral hepatitis and trematode (liver fluke) infections.

摘要

据报道,疟疾感染会损害肝脏药物清除能力,并导致啮齿动物和人类中细胞色素P450(CYP)介导的单加氧酶活性下调。在本研究中,我们调查了伯氏疟原虫感染对雌性DBA/2和C57BL/6小鼠肝脏单加氧酶活性的影响。在这两种小鼠品系中,伯氏疟原虫感染均降低了由CYP1A(乙氧基异吩恶唑酮-O-脱乙基酶:DBA/2为65.3%,C57BL/6为44.7%)和2B(苄氧羰基苯并芘-O-脱甲基酶:DBA/2为64.3%,C57BL/6为49.8%)亚家族同工型介导的活性,并增加了由2A5(香豆素-7-羟化酶:DBA/2为182.4%,C57BL/6为148.5%)和2E1(对硝基苯芐基醚脱苯甲基酶:DBA/2为177.8%,C57BL/6为128.5%)同工型介导的活性,与未感染的对照组相比。由于疟疾感染还导致血清中谷丙转氨酶(ALT)(273.1%)和谷草转氨酶(AST)(354.1%)活性增加,我们的研究结果与CYP2A5活性由肝损伤诱导的观点一致。在许多感染和炎症刺激中发现了CYP介导活性几乎普遍的降低,但之前仅在一些病毒性肝炎和吸虫(肝吸虫)感染中注意到CYP2A5的诱导。

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