PMID- 31353066
OWN - NLM
STAT- MEDLINE
DCOM- 20200227
LR  - 20200227
IS  - 1879-0070 (Electronic)
IS  - 0732-8893 (Linking)
VI  - 95
IP  - 3
DP  - 2019 Nov
TI  - Antiparasitic effect of (-)-alpha-bisabolol against Trypanosoma cruzi Y strain forms.
PG  - 114860
LID - S0732-8893(19)30644-3 [pii]
LID - 10.1016/j.diagmicrobio.2019.06.012 [doi]
AB  - 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 (-)-alpha-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.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - de Menezes, Ramon R P P B
AU  - de Menezes RRPPB
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil. Electronic address: ramonppessoa@gmail.com.
FAU - Sampaio, Tiago L
AU  - Sampaio TL
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Lima, Danya B
AU  - Lima DB
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Sousa, Paloma L
AU  - Sousa PL
AD  - Chemistry Institute, Sao Paulo University, Sao Paulo, Brazil.
FAU - de Azevedo, Isabella E P
AU  - de Azevedo IEP
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Magalhaes, Emanuel P
AU  - Magalhaes EP
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Tessarolo, Louise D
AU  - Tessarolo LD
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Marinho, Marcia Machado
AU  - Marinho MM
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil.
FAU - Dos Santos, Ricardo Pires
AU  - Dos Santos RP
AD  - Computer Engineering, Federal University of Ceara, Sobral, Ceara, Brazil.
FAU - Martins, Alice M C
AU  - Martins AMC
AD  - Department of Clinical and Toxicological Analysis, Federal University of Ceara, 
      Fortaleza, Ceara, Brazil. Electronic address: martinsalice@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190628
PL  - United States
TA  - Diagn Microbiol Infect Dis
JT  - Diagnostic microbiology and infectious disease
JID - 8305899
RN  - 0 (Monocyclic Sesquiterpenes)
RN  - 0 (Trypanocidal Agents)
RN  - 24WE03BX2T (bisabolol)
RN  - EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating))
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chagas Disease/drug therapy/parasitology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/antagonists & 
      inhibitors/metabolism
MH  - Inhibitory Concentration 50
MH  - Macaca mulatta
MH  - Molecular Docking Simulation
MH  - Molecular Structure
MH  - Monocyclic Sesquiterpenes/chemistry/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Trypanocidal Agents/*pharmacology
MH  - Trypanosoma cruzi/*drug effects/physiology
OTO - NOTNLM
OT  - Apoptosis
OT  - Bisabolol
OT  - Trypanosoma cruzi
EDAT- 2019/07/30 06:00
MHDA- 2020/02/28 06:00
CRDT- 2019/07/30 06:00
PHST- 2018/07/16 00:00 [received]
PHST- 2019/05/20 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2020/02/28 06:00 [medline]
PHST- 2019/07/30 06:00 [entrez]
AID - S0732-8893(19)30644-3 [pii]
AID - 10.1016/j.diagmicrobio.2019.06.012 [doi]
PST - ppublish
SO  - Diagn Microbiol Infect Dis. 2019 Nov;95(3):114860. doi: 
      10.1016/j.diagmicrobio.2019.06.012. Epub 2019 Jun 28.