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

Plasmodium berghei (ANKA):: Infection induces CYP2A5 and 2E1 while depressing other CYP isoforms in the mouse liver
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DOI:
10.1016/j.exppara.2006.01.013
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发表时间:
2006-08-01
影响因子:
2.1
通讯作者:
Pauragartten, Francisco J. R.
Pauragartten, Francisco J. R.
中科院分区:
医学4区
文献类型:
--
作者:
De-Oliveira, Ana C. A. X.;Da-Matta, Anndressa C.;Pauragartten, Francisco J. R.

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据报道,疟疾感染会损害啮齿动物和人类的肝脏药物清除率,并导致 CYP 介导的单加氧酶活性下调。在本研究中,我们研究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。在两种小鼠品系中,伯氏疟原虫感染均降低了 CYP1A(EROD:DBA/2 65.3%、C57BL/6 44.7%)和 2B(BROD:DBA/2 64.3%、C57BL/6 49.8%)亚科异构体介导的活性,并增加了 2A5(COH:DBA/2 182.4%、与未感染对照相比,C57BL/6 148.5%) 和 2E1 (PNPH: DBA/2 177.8%, C57BL/6 128.5%) 同工型。由于疟疾感染还导致血清中 ALT (273.1%) 和 AST (354.1%) 活性增加,因此我们的研究结果与 CYP2A5 活性是由肝损伤诱导的观点一致。在许多感染和炎症刺激下发现 CYP 介导的活性几乎普遍降低,但之前仅在某些病毒性肝炎和吸虫(肝吸虫)感染中发现了 CYP2A5 的诱导。 (c) 2006 Elsevier Inc. 保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.