title: Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection.
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.
authors.affiliation: 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.|The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kume
authors.affiliation: 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.
authors.forename: Maria Shirley
authors.initials: MS
authors.lastname: Herbas
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 573-8577, Japan.
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 573-8577, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishida
authors.affiliation: 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. hisuzuki@obihiro.ac.jp.|The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan. hisuzuki@obihiro.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use; D001599:Berberine / Q000627:therapeutic use; D002792:Cholestyramine Resin / Q000627:therapeutic use; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000188:drug therapy; D010967:Plasmodium yoelii / Q000187:drug effects; D011341:Probucol / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D014811:Vitamin E Deficiency / Q000139:chemically induced / Q000150:complications*; D024502:alpha-Tocopherol / Q000097:blood*
chemical_list: D000924:Anticholesteremic Agents; D000962:Antimalarials; D001599:Berberine; D002792:Cholestyramine Resin; D000069438:Ezetimibe; D024502:alpha-Tocopherol; D011341:Probucol
keywords: Alpha-tocopherol; Anti-hyperlipidemia drugs; Malaria; Plasmodium yoelii; Probucol