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疟疾与青蒿素联合疗法中的氧化应激:利弊

Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons.

作者信息

Kavishe Reginald A, Koenderink Jan B, Alifrangis Michael

机构信息

Department of Biochemistry & Molecular Biology, Faculty of Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania.

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

FEBS J. 2017 Aug;284(16):2579-2591. doi: 10.1111/febs.14097. Epub 2017 May 25.

Abstract

Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug. Although the exact mechanisms of action of artemisinins are not well understood, several studies have proposed multiple cellular targets of artemisinins with involvement of reactive oxygen species (ROS). Most of the currently used ACT partner drugs are also known to involve ROS production in their mechanisms of action. This review gives a brief account of the oxidative stress and redox systems in malaria and discusses the context of antimalarial effectiveness of different ACTs compared with monotherapies of the partner drugs. A final account on the Pros and Cons of ACT as a strategy is discussed.

摘要

以青蒿素为基础的联合疗法(ACT)已被采用作为一种策略,以减轻对抗疟单一疗法的多重耐药性。ACT将青蒿素衍生物快速有效但血浆半衰期较短的抗疟作用与一种作用时间更长的伙伴药物相结合。尽管青蒿素的确切作用机制尚未完全明确,但多项研究提出了青蒿素的多个细胞靶点,且涉及活性氧(ROS)。目前大多数使用的ACT伙伴药物在其作用机制中也已知会涉及ROS的产生。本综述简要介绍了疟疾中的氧化应激和氧化还原系统,并讨论了与伙伴药物单一疗法相比,不同ACT抗疟有效性的相关情况。最后讨论了ACT作为一种策略的优缺点。

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