ANTIPARASITIC ACTIVITY OF ABIETANE AGAINST LEISHMANIA AMAZONENSIS

TRONCOSO M.; GERMANÓ, MJ; ARRIETA, V.; GARCÍA BUSTOS, MF.; CIFUENTES, D.; CARGNELUTTI, DE.; LOZANO, E.

San Juan

Congreso; XLI Reunión Científica Anual de la Sociedad de Biología de Cuyo.; 2023

Sociedad de Biología de Cuyo

The leishmaniases are a spectrum of diseases caused by infection with protozoan pathogens of the Leishmania genus, with an estimated 2 million new cases per annum. Leishmania parasites are transmitted to a mammalian host via the bite of an infected sand fly. The clinical forms of the disease (cutaneous, mucocutaneous and visceral leishmaniasis) depend on the species of Leishmania involved. In Argentina, affects the northern region of the country with an incidence that has increased over the last two decades. Current treatments for leishmaniasis are unsatisfactory due to high associated toxicity, cost, complex administration and the emergence of resistant strains. Efforts have greatly increased over the last decade to identify novel compounds with anti-leishmanial properties. Thus, one strategy in the search for new compounds is the screening of molecules purified from plant sources. Terpenes appear as good candidates, because they are abundant in the plant kingdom and some of them have shown a significant activity against trypanosomatids. The terpene Abietane (HABTO), isolated from Salvia cuspidata, was tested against Leishmania amazonensis. We evaluate the effect of HABTO in an in vitro model and in vivo model of cutaneous leishmaniasis. The treatment with HABTO induced a significant increase in ROS levels in L. amazonensis promastigotes compared to controls. We measured ROS using the probe 2',7'-Diclocrofluorescein diacetate. Moreover, HABTO produces a significant reduction in the mitochondrial activity of promastigotes, evaluated with MTT. In promastigotes treated with HABTO there was a decrease in the inner concentration of GSH within the parasites. Male BALB/c mice were infected in the right footpad with 1x105 promastigotes of L (L.) amazonensis and localy treated, once a week for 4 weeks, with 1 mg/animal/day of HABTO. We observe that the treatment with the terpene decreases footpad swelling compared to the controls. This is related to the significant decrease in parasite load, splenic index and IgG levels observed with every treatment. Moreover, the high IgG2a and low IgG1 levels of anti-Leishmania antibodies, observed after HABTO treatment, are associated with protective immunity against different Leishmania species. Although we consider it necessary to carry out more research on this terpene, our findings suggest that HABTO could be considered as possible novel candidate to be used as therapeutic agent against L. amazonensis and thus treat cutaneous leishmaniasis.