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Effect of α-Tocopheryloxy Acetic Acid on the Infection of Mice with Plasmodium berghei ANKA In Vivo and Humans with P. falciparum In Vitro

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Abstract

Purpose

Malarial parasites are susceptible to oxidative stress. The effects of α-tocopheryloxy acetic acid (α-TEA), a vitamin E analog, on infection by Plasmodium berghei ANKA and P. falciparum in mice and human red blood cells (RBCs), respectively, were examined in this study.

Methods

For in vivo studies in mice, RBCs infected with P. berghei ANKA were inoculated via intraperitoneal injection and α-TEA was administered to C57BL/6 J male mice after infection. The blood–brain barrier (BBB) permeability was examined by Evans blue staining in experimental cerebral malaria at 7 days after infection. The in vitro inhibitory effect of α-TEA on P. falciparum 3D7 (chloroquine-sensitive strain) and K1 (multidrug-resistant strain) was tested using a SYBR Green I-based assay.

Results

When 1.5% α-TEA was administered for 14 days after infection, 88% of P. berghei ANKA-infected mice survived during the experimental period. Nevertheless, all the control mice died within 12 days of infection. Furthermore, the Evans blue intensity in α-TEA-treated mice brains was less than that in untreated mice, indicating that α-TEA might inhibit the destruction of the BBB and progression of cerebral malaria. The in vitro experiment revealed that α-TEA inhibited the proliferation of both the 3D7 and K1 strains.

Conclusion

This study showed that α-TEA is effective against murine and human malaria in vivo and in vitro, respectively. Although α-TEA alone has a sufficient antimalarial effect, future research could focus on the structure–activity relationship to achieve better pharmacokinetics and decrease the cytotoxicity and/or the combined effect of α-TEA with existing drugs. In addition, the prophylactic antimalarial activity of premedication with α-TEA may also be an interesting perspective in the future.

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Availability of Data and Material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Editage (www.editage.com) for English language editing.

Funding

A part of this work was supported by grant from the Naito Foundation.

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Author notes

  1. Nanang R. Ariefta and Aiko Kume contributed equally to this work.

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, Obihiro, Hokkaido, 080-8555, Japan

    Nanang R. Ariefta, Aiko Kume, Yoshifumi Nishikawa, Tomoyo Taniguchi, Rika Umemiya-Shirafuji, Shunji Kasai & Hiroshi Suzuki

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  1. Nanang R. Ariefta
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Contributions

The research was designed by HS, AK, YN, and SK. Laboratory experiments were performed by NA and AK The manuscript was written by HS, TT, YN, and RU-S. All the authors have read and agreed to the published version of the manuscript.

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Correspondence to Hiroshi Suzuki.

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The animals used in this study were treated and cared for based on the Guiding Principles for the Care and Use of Research Animals established by Obihiro University of Agriculture and Veterinary Medicine. All animal experimental protocols were approved by the Institutional Animal Ethics Committee, Obihiro University of Agriculture and Veterinary Medicine.

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Ariefta, N.R., Kume, A., Nishikawa, Y. et al. Effect of α-Tocopheryloxy Acetic Acid on the Infection of Mice with Plasmodium berghei ANKA In Vivo and Humans with P. falciparum In Vitro. Acta Parasit. 67, 1514–1520 (2022). https://doi.org/10.1007/s11686-022-00604-7

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