Vinpocetine increases the microsporicidal effect of albendazole on encephalitozoon intestinalis.

ABSTRACT

Microsporidia are obligate, intracellular, spore-forming eukaryotic fungi, infect humans and animals. In the treatment of disseminated microsporidiosis albendazole is the choice of drug. In recent years, antiparasitic activity of phosphodiesterase (PDE) enzyme inhibitors has been demonstrated against paracites and fungi, however, there is no information on microsporidia. Vinpocetine is currently used as a cerebral vasodilator drug and also as a dietary supplement to improve cognitive functions. Vinpocetine inhibits PDE1, so we aimed to investigate whether vinpocetine alone or in combination with albendazole has any effect on the spore load of Encephalitozoon intestinalis (E. intestinalis)-infected HEK293 cells. After determining the noncytotoxic concentrations of vinpocetine and albendazole on the host cell by MTT assay, HEK293 cells were infected with E. intestinalis spores. Then, two different concentrations of vinpocetine, albendazole, and combination of both drugs were applied to the cells with an interval of 72 hours for 15 days. Spore load of the cells was analysed by real time-PCR. After the last treatment, spore DNA load was significantly reduced only in the group treated with 14 ng/mL albendazole. It was not different from control in groups treated with 7 ng/mL albendazole and 4 - 20 µM vinpocetine. However, the combination of vinpocetine significantly increased the effect of albendazole at both concentrations. To our knowledge, this is the first study to investigate the microsporicidal activity of vinpocetine as well as its combinations with albendazole. However, further studies are needed to investigate the mechanism of action and also confirm in vivo conditions.

E. intestinalis, common cause of microsporidia-associated diseases in humans, Albendazole is used in the treatment of E. intestinalis infection, Vinpocetine inhibits PDE1 and voltage-gated Ca2+ channels, Vinpocetine significantly enhanced the effect of albendazole on E. intestinalis spore DNA load.