Evaluation of terbinafine treatment in Leishmania chagasi-infected hamsters (Mesocricetus auratus).

The objective of the present study was to assess the effect of terbinafine treatment in hamsters infected with Leishmania chagasi. Four of five groups of hamsters were infected with 3 x 10(7) L. chagasi promastigotes by the intracardiac route and submitted to different treatments of 30 days duration starting on the 30th day after inoculation. Group 1 was treated with 100mg/kg terbinafine PO, group 2 was treated with 80 mg/kg Glucantime IM, and group 3 was treated with a combination of the same dose of each drug by the same routes. Group 4 (control) received vehicle (Tween 80 [0.1%]+CMC[0.5%]+H(2)O [0.5 ml], PO). Spleen parasite burden and spleen relative weight were determined 3 days after the end of the treatment. The results were analyzed by the Kruskal-Wallis test (P < 0.05). There was no difference between the infected untreated and terbinafine-treated groups in spleen parasite burden (15.81+/-15.81 vs. 13.00+/-12.94, respectively). Terbinafine plus Glucantime (6.11+/-5.90) and Glucantime alone (4.83+/-4.82) significantly reduced spleen parasite burden compared to the infected untreated group (15.81+/-15.81, P<0.01). There was a difference in the relative weight of the spleen between the naïve and the infected untreated groups (2.5+/-0.2 vs. 9.8+/-1.0, respectively) as well as between the naïve and terbinafine groups (2.5+/-0.2 vs. 10.0+/-1.4, respectively). Glucantime alone and Glucantime plus terbinafine (2.5+/-0.2 and 4.2+/-0.6) significantly reduced the weight of the spleen in comparison with the infected untreated group. Even so, the spleen parasite burden was directly related to spleen weight. Terbinafine alone at the dose and schedule used had no effect on spleen parasite burden or relative spleen weight of L. chagasi-infected hamsters.

In vitro and in vivo Leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol).

This study aims to evaluate the in vitro and in vivo leishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam(R)). These compounds (0.0125-4.0 mg/mL) were evaluated in vitro against intracellular amastigotes of Leishmania (Viannia) braziliensis (LVb), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro, lapachol exhibited an anti-amastigote effect, whereas in vivo it did not prevent the development of LVb-induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam(R) demonstrated a significant anti-amastigote effect in vitro for LVb and apparent clinical cure in vivo (60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitro without offering significant protection against LVb-infected lesions in hamsters suggests that lapachol in vivo might possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study.