Effect of α-tocopheryloxyacetic acid, a mitocan, on mice infected with Trypanosoma congolense.

The genus Trypanosoma is vulnerable to oxidative stress, and reactive oxygen species (ROS) suppress Trypanosoma proliferation. We investigated the effects of alpha-tocopheryloxyacetic acid (α-TEA), a stable vitamin E-derived mitocan, on the course of Trypanosoma congolense IL-3000 infection in mice and in an in vitro culture. C57BL/6 J male mice infected with 3 × 104 T. congolense IL-3000 cells were fed a 0.25% or 0.75% α-TEA diet for 7 or 28 days from day 3 of infection. The survival duration of all of the α-TEA-treated mice was significantly longer than that of the control mice fed a regular diet (p < 0.05). Similar results were obtained when α-TEA (14 mg/day) was orally administered to mice via a feeding needle 1×/day for 5 days from day 3 after infection; we then observed that α-TEA effectively inhibited the growth of T. congolense in a dose-dependent manner (p < 0.05). To assess the mechanisms of action of α-TEA, we conducted annexin V (AV)/propidium iodide (PI) labeling and a JC-1 labeling lactate assay, plus a 2',7'-dichlorofluorescein diacetate (DCFH-DA)/mtSOX Deep Red (mtSOX) labeling assay. Treatment with α-TEA induced the apoptosis of T. congolense, decreased the mitochondrial membrane potential (p < 0.05), and produced ROS in mitochondria (p < 0.05). Thus, α-TEA directly suppressed the proliferation of T. congolense in mice by stimulating a mitochondrion of T. congolense to produce ROS. These results indicate that α-TEA might be a potent candidate ingredient for an oral drug to treat the parasitic infection trypanosomiasis, with new mechanisms of action.