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Antiparasitic effect of (-)-α-bisabolol against Trypanosoma cruzi Y strain forms.
de Menezes, Ramon R P P B; Sampaio, Tiago L; Lima, Danya B; Sousa, Paloma L; de Azevedo, Isabella E P; Magalhães, Emanuel P; Tessarolo, Louise D; Marinho, Márcia Machado; Dos Santos, Ricardo Pires; Martins, Alice M C.
Afiliación
  • de Menezes RRPPB; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: ramonppessoa@gmail.com.
  • Sampaio TL; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Lima DB; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Sousa PL; Chemistry Institute, São Paulo University, São Paulo, Brazil.
  • de Azevedo IEP; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Magalhães EP; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Tessarolo LD; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Marinho MM; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
  • Dos Santos RP; Computer Engineering, Federal University of Ceará, Sobral, Ceará, Brazil.
  • Martins AMC; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: martinsalice@gmail.com.
Diagn Microbiol Infect Dis ; 95(3): 114860, 2019 Nov.
Article en En | MEDLINE | ID: mdl-31353066
Chagas disease is caused by Trypanosoma cruzi and affects about 7 million people worldwide. Benznidazole and nifurtimox have low efficacy and high toxicity. The present study was designed to identify the trypanocidal effect of (-)-α-Bisabolol (BIS) and investigate its mechanism. Epimastigotes and trypomastigotes were cultured with BIS and the viable cells were counted. BIS antiamastigote effect was evaluated using infected LLC-MK2 cells. MTT assay was performed to evaluate BIS cytotoxicity. Growth recovery was assessed to evaluate BIS effect after short times of exposure. BIS mechanism was investigated through flow cytometry, with 7-AAD and Annexin V-PE. DCFH-DA, rhodamine 123 (Rho123) and acridine orange (AO). Finally, enzymatic and computational assays were performed to identify BIS interaction with T. cruzi GAPDH (tcGAPDH). BIS showed an inhibitory effect on epimastigotes after all tested periods, as well on trypomastigotes. It caused cytotoxicity on LLC-MK2 cells at higher concentrations, with selectivity index (SeI) = 26.5. After treatment, infected cells showed a decrease in infected cells, the number of amastigotes per infected cell and the survival index (SuI). Growth recovery demonstrated that BIS effect causes rapid death of T. cruzi. Flow cytometry showed that BIS biological effect is associated with apoptosis induction, increase in cytoplasmic ROS and mitochondrial transmembrane potential, while reservosome swelling was observed at a late stage. Also, BIS action mechanism may be associated to tcGAPDH inhibition. Altogether, the results demonstrate that BIS causes cell death in Trypanosoma cruzi Y strain forms, with the involvement of apoptosis and oxidative stress and enzymatic inhibition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tripanocidas / Trypanosoma cruzi / Sesquiterpenos Monocíclicos Límite: Animals Idioma: En Revista: Diagn Microbiol Infect Dis Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tripanocidas / Trypanosoma cruzi / Sesquiterpenos Monocíclicos Límite: Animals Idioma: En Revista: Diagn Microbiol Infect Dis Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos