Abstract
Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. 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. 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. (L.) amazonensis, mice macrophages infected with L. (L.) amazonensis, and in vivo tests in BALB/c mice infected with L. (L.) amazonensis. We demonstrated that TUB–NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.
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Acknowledgements
This work was supported by CNPq (473.121/2004-2), FAPESP (00/10016-1 and 06/04656-4), LIM-48 (FM-USP) and by fellowships from CNPq (P.C.C.), CAPES (J.I.A.), and FAPESP (D.C.C.R.). All procedures in this study are in accordance with the Brazilians laws and complied with the ethical guidelines of the institution for experiments with animals. The in vivo analyses were conducted according to the Guide for the “Care and Use of Laboratory Animals” from the National Academy of Sciences (http://www.nap.edu).
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Aoki, J.I., Yamashiro-Kanashiro, E.H., Ramos, D.C.C. et al. Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport. Parasitol Res 104, 223–228 (2009). https://doi.org/10.1007/s00436-008-1177-z
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DOI: https://doi.org/10.1007/s00436-008-1177-z