Journal
ASIAN PACIFIC JOURNAL OF TROPICAL MEDICINE
Volume 9, Issue 7, Pages 633-638Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.1016/j.apjtm.2016.05.018
Keywords
Leishmaniosis; Hypoxia inducible factor; Resveratrol; Echinomycin; CdCl2; Mimosine
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil [2009/10771-9]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil [301052/2009-3]
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Objective: To evaluate whether hypoxia inducible factor (HIF-1 alpha) targeting pharmacological drugs, echinomycin, resveratrol and CdCl2, which inhibit HIF-1 alpha stimulation, and mimosine, which enhances the stability of HIF-1 alpha present antileishmanial properties. Methods: The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis. Results: Resveratrol and CdCl2, reduced the parasite load [IC50, (27.3 +/- 2.25) mu M and (24.8 +/- 0.95) mu M, respectively]. The IC50 value of echinomycin was (22.7 +/- 7.36) mu M and mimosine did not alter the parasite load in primary macrophages. The macrophage viability IC50 values for resveratrol, echinomycin and CdCl2, and mimosine were >40 mu M, >100 mu M > 200 mu M and>2 000 mu M, respectively. In vivo no differences between cutaneous lesions from control, resveratrol- and echinomycin-treated Balb/c mice were detected. Conclusions: Resveratrol, echinomycin and CdCl2, reduce parasite survival in vitro. The HIF-1 alpha targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies.
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