Probucol-Induced ?-Tocopherol Deficiency Protects Mice against Malaria Infection.

ABSTRACT: The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of ?-tocopherol transfer protein knockout mice showing undetectable plasma levels of ?-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced ?-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma ?-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by ?-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing ?-tocopherol deficiency without dietary ?-tocopherol restriction.

SUBMITTER: Herbas MS 

PROVIDER: S-EPMC4546625 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature