Sodium Diethyldithiocarbamate antiparasitic activity against different Trypanosoma cruzi strains: Insights of its biological activity

Oliveira, J.; Torres, T. M.; Moreno, C.; Amorim-Carmo, B.; Damasceno, I.; Soares, A. K.; Barbosa, J. d. S.; Rocha, H. A.; Silva, M. S.

doi:10.1101/2020.07.06.189233

bioRxiv · 10.1101/2020.07.06.189233

Sodium Diethyldithiocarbamate antiparasitic activity against different Trypanosoma cruzi strains: Insights of its biological activity

Oliveira, J.·Torres, T. M.·Moreno, C.·Amorim-Carmo, B.·Damasceno, I.·Soares, A. K.·Barbosa, J. d. S.·Rocha, H. A.·Silva, M. S.

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Abstract

BackgroundChagas disease is caused by the protozoan Trypanosoma cruzi, a neglected tropical disease that affects thousands of people, mainly in Latin America. The drugs currently used in therapy are toxic and have therapeutic limitations during treatment. In addition, the genetic diversity of T. cruzi represents an important variable and challenge with regard to the pathogenesis of the infection, the epidemiological profile of the cases, and the therapeutic control of the infection. Sodium diethyldithiocarbamate (DETC) is a compound of high pharmacological versatility acting as metal chelators and producing reactive oxygen species. Thus, the objective of this work is to characterize the antiparasitic action of DETC against different strains and evolutionary forms of T. cruzi, as well as the characterization of the mechanism of antiparasitic action. Methodology/Principal findingsThe different strains and evolutionary forms of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, the evolutionary forms epimastigote and trypomastigote of T. cruzi were used by resazurin reduction methods and by counting under optical microscopy. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 {+/-} 3,181{micro}M to 60.49 {+/-} 7.62 {micro}M. Cell cytotoxicity against cell lines 3T3 and RAW and evaluated by MTT, demonstrated that DETC in high concentration (2222 {micro}M) reduces around 60% the cell capacity of MTT reduction. The antiparasitic activity of DETC has been demonstrated through damage caused in the mitochondria of T. cruzi, a reduction of up to 80% in the mitochondrial potential of the parasites, as well as through damage caused in the membrane of the parasite. ConclusionIn this study we can conclude that DETC has antiparasitic activity against different genotypes and evolutionary forms of T. cruzi, representing a promising molecule as a drug for the treatment of Chagas disease.

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Oliveira, J., Torres, T. M., Moreno, C., Amorim-Carmo, B., Damasceno, I., Soares, A. K., Barbosa, J. d. S., Rocha, H. A., Silva, M. S.. 2020-07-06. Sodium Diethyldithiocarbamate antiparasitic activity against different Trypanosoma cruzi strains: Insights of its biological activity. https://doi.org/10.1101/2020.07.06.189233

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