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α-Tocopheryl succinate-suppressed development of cerebral malaria in mice

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Abstract

α-Tocopheryl succinate (α-TOS), a derivative of vitamin E, is synthesized by esterification of α-tocopherol. It has been reported that α-TOS inhibits the mitochondrial complex II resulting in generation of reactive oxygen species, which triggers selective apoptosis in a large number of cancer cells, while it appears largely non-toxic towards normal cells. Plasmodium parasites are well known to have high sensitivity to oxidative stress. Thus, α-TOS is suspected to impact Plasmodium parasites by oxidative stress. In this study, to ascertain whether α-TOS is an appropriate candidate for an anti-malarial drug, C57BL/6J mice were infected with P. yoelii 17XL and P. berghei ANKA, a lethal strain of rodent malaria and experimental cerebral malaria (ECM), and treated with several concentrations of α-TOS by intraperitoneal administration on 1, 3, 5, and 7 days post infection (dpi). In addition, the permeability of the blood brain barrier (BBB) was examined by Evans blue staining in ECM on 7 dpi. As a result of α-TOS treatment, parasitemia was decreased and survival rate was significantly increased in mice infected with both parasites. Furthermore, the intensity of Evans blue staining on brains taken from α-TOS-treated mice was weaker than that of untreated mice. This means that α-TOS might inhibit the breakdown of BBB and progress of cerebral malaria. These findings indicate that vitamin E derivatives like α-TOS might be a potential candidate for treatment drugs against malaria.

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Acknowledgements

We thank Dr. PF ADJOU MOUMOUNI at the National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, for language editing. A part of this work was supported by grant from the Naito Foundation.

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  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, Hana Furuya & Hiroshi Suzuki

  2. Eisai Co., Ltd., 13-1 Nishigoken-cho, Shinjuku-ku, Tokyo, 162-0812, Japan

    Shunji Kasai

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  1. Aiko Kume
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  2. Shunji Kasai
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Correspondence to Hiroshi Suzuki.

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Kume, A., Kasai, S., Furuya, H. et al. α-Tocopheryl succinate-suppressed development of cerebral malaria in mice. Parasitol Res 117, 3177–3182 (2018). https://doi.org/10.1007/s00436-018-6016-2

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