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Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection

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Abstract

The current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. However, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. Previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. Here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and probucol to modify the host plasma alpha-tocopherol concentration. The drugs were mixed with diet and fed to C57BL/6J mice for 2 weeks. Although all drugs reduced plasma alpha-tocopherol concentration after 2 weeks of feeding, probucol-treated mice showed 90 % reduction and it was the lowest alpha-tocopherol concentration among the four drugs. Ezetimibe, berberine, and combination of ezetimibe and berberine pretreatment for 2 weeks were not effective against infection of Plasmodium yoelii XL17, a lethal strain, for survival and parasitemia in mice. Two-week pretreatment and 1-week treatment after infection of cholestyramine had also no effect on malaria infection. Survival rates of cholestyramine, ezetimibe, and/or berberine treated mice were 0–22 %. However, probucol caused significant decrease in parasitemia and increased in mice survival following 2-week pretreatment and 1-week treatment after infection. All control mice died while all probucol treated mice survived during the course of infection. Thus, probucol which reduced plasma alpha-tocopherol concentration was effective in enhancing the host to resist malaria infection in mice. Our finding indicates that plasma alpha-tocopherol reducing drugs like probucol might be a candidate for beneficial prevention strategy for travelers from malaria-free area.

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Authors and Affiliations

  1. Research Unit for Functional Genomics, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan

    Aiko Kume, Maria Shirley Herbas & Hiroshi Suzuki

  2. The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Aiko Kume & Hiroshi Suzuki

  3. Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 573-8577, Japan

    Mototada Shichiri & Noriko Ishida

Authors
  1. Aiko Kume
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  2. Maria Shirley Herbas
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  3. Mototada Shichiri
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  4. Noriko Ishida
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  5. Hiroshi Suzuki
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Correspondence to Hiroshi Suzuki.

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Kume, A., Herbas, M.S., Shichiri, M. et al. Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection. Parasitol Res 115, 69–75 (2016). https://doi.org/10.1007/s00436-015-4722-6

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  • DOI: https://doi.org/10.1007/s00436-015-4722-6

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