5 years ago

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

Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons
Jan B. Koenderink, Michael Alifrangis, Reginald A. Kavishe
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. Malaria is characterized with oxidative stress derived from both the parasite's metabolism and the host immune response. Some antimalarial drugs increase oxidative stress. While oxidative stress can help eliminate parasites, it can also exacerbate the pathology. This article reviews oxidative stress in view of the current artemisinin-based combination therapies in malaria.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14097

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