Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB-NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania (L.) amazonensis, Leishmania (L.) chagasi, Leishmania (L.) major, and Leishmania (V.) braziliensis as well as in cultures of amastigote forms of L. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma gambiense. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. (L.) amazonensis, controlling infection progression and limiting dissemination.

These results suggest that CM modulates experimental infection by L. CM treatment also decreased parasite load in the regional popliteal lymph nodes and in the spleen. (L.) amazonensis in the paws, resulting in smaller lesions. In the in vivo infection, when administered, orally or subcutaneously in mice, CM reduced infection by L. The in vitro results showed that at 40% CM reduced the infection index, and induced NO production in the elicited macrophages, which suggests that the inhibitory effect on infection index may be mediated by NO. The progression of the lesions was examined over a 9-week period by measuring footpad swelling, and the parasite load in regional lymph nodes and spleen. (L.) amazonensis promastigotes injected in to the right hind footpad (25 microl in phosphate buffered saline). The in vivo tests were performed in mice infected with 10(7)L. The effect of CM on macrophages leishmanicidal activity in 24 and 48 h cultures was evaluated by determining infection index and measuring nitric oxide (NO) production. Twenty-four hours later, the macrophages were infected with Leishmania amastigotes in culture medium.

For the in vitro tests, Balb/c mouse peritoneal macrophages (5x10(5) cells in 500 microl of culture medium, supplemented with 10% fetal calf serum, penicillin (100 U/ml) and streptomycin (0.1 mg/ml) (were distributed in 24-well plates and CM was added at concentrations of 20 or 40%. This study investigates the action of Canova medication (CM) on experimental infection by Leishmania (Leishmania) amazonensis, utilizing in vitro and in vivo assays.

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