American Leishmania spp: Formycin B treatment of cutaneous leishmaniasis in mice

Abstract

Using foot-pad infection of female C57BL/6, DBA/2J and NMRI-IVIC mice as an animal model for American cutaneous leishmaniasis (ACL), we evaluated the inhibitory effect of Formycin B (FoB) on the infection produced by 7 different Leishmania isolates. When treatment was initiated some days, or even some weeks, after infection a significant leishmanistatic effect was detected on mice infected with all Leishmania isolates, which reached 30-55 weeks for some isolates. The optimal dose schedule was 1.25 mg/kg body weight/day, injected intraperitoneally for 20 consecutive days. Significant differences in the sensitivity of various Leishmania spp. to FoB were found, either in vivo, or in vitro where a high [3H]FoB incorporation rate was found only for certain Leishmania isolates. The low toxicity of this drug and the sensitivity of the 7 Leishmania isolates tested suggest that FoB could be useful in the treatment of ACL.

The interactions between drugs and the parasite surface

“…Different strains of a single parasite or of closely related species may vary in their rates of drug uptake. For instance, a recent study on strains of American Leishmania species (L. mexicana, L. braziliensis and L. garnhami) demonstrates unequivocally that different isolates can vary in their rates of uptake of formycin B (Rojas & Avila, 1987). Furthermore, with intracellular parasites specific drug targeting to both host cell and parasite surface membranes may be necessary to effect delivery of therapeutic levels of drug to the parasite itself.…”

Avaliação do efeito antiparasitário do omeprazol na prevenção do desenvolvimento de lesões cutâneas em hamsters infectados por Leishmania brasiliensis

“…À medida que se compreendem as características moleculares dos mecanismos de defesa e sobrevivência de agentes infecciosos, abrem-se possibilidades de pesquisa para o desenvolvimento de agentes que interfiram em seu ciclo vital. 2,7,8 A pesquisa de agentes leishmanicidas de baixa toxicidade, alta eficácia e comodidade posológica é um desafio que tem envolvido diversos grupos de pesquisa ao redor do mundo. 3,[9][10][11][12][13] A redução de mais de 90% dos parasitas (Leishmania donovani) em culturas ácidas ou no interior de macrófagos in vitro empregando meios com diferentes concentrações de ommeprazol é um exemplo de interferência molecular direta no ciclo de vida do protozoário.…”