TY - JOUR
T1 - Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi
AU - de Freitas Oliveira, Johny Wysllas
AU - Torres, Taffarel Melo
AU - Moreno, Cláudia Jassica Gonçalves
AU - Amorim-Carmo, Bruno
AU - Damasceno, Igor Zumba
AU - Soares, Ana Katarina Menezes Cruz
AU - da Silva Barbosa, Jefferson
AU - Rocha, Hugo Alexandre Oliveira
AU - Silva, Marcelo Sousa
N1 - Funding Information:
This research was funded by Global Health and Tropical Medicine: Grant number IHMT-UID/multi/04413/2013 and Grant number PTDC/CVT-CVT/28908/2017, FCT-Portugal.
Funding Information:
We would like to thank Prof. João Aristeu da Rosa and Dr. Aline Rimodi Rimeiro at UNESP (Universidade Estadual de São Paulo) Araraquara (Brazil) for offering four different strains of T. cruzi. JWFO, CJGM, and BAC thanks to the financial support (PhD and Post-doctoral fellowships) provided by Capes/Brazil; MSS and HAOR thanks to CNPq/Brazil for the Research Grant (Bolsa de Produtividade). We also would like to thank the Department of Materials Engineering at UFRN for allowing the use of their scanning electron microscope, and the Department of Biochemistry at UFRN for allowing the use of their Flow Cytometer. We are also grateful to Paulo Fanado for editing this manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.
AB - Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.
UR - http://www.scopus.com/inward/record.url?scp=85106986406&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-90719-0
DO - 10.1038/s41598-021-90719-0
M3 - Article
C2 - 34045624
AN - SCOPUS:85106986406
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11200
ER -
