| Author | Inacio, Job D. F. | |
| Author | Fonseca, Myslene S. | |
| Author | Sousa, Gabriel Limaverde | |
| Author | Tomas, Ana M. | |
| Author | Castro, Helena | |
| Author | Amaral, Elmo E. Almeida | |
| Access date | 2021-04-30T18:08:37Z | |
| Available date | 2021-04-30T18:08:37Z | |
| Document date | 2021 | |
| Citation | INACIO, Job D. F. et al. Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death. Front. Cell. Infect. Microbiol., v. 11, Article 640561, 11p, Mar. 2021. | pt_BR |
| ISSN | 2235-2988 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/46985 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmania infantum | pt_BR |
| Subject in Portuguese | Reductase trypanothione | pt_BR |
| Subject in Portuguese | Mecanismo de ação | pt_BR |
| Subject in Portuguese | Inibidor competitivo | pt_BR |
| Title | Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death | pt_BR |
| Type | Article | |
| DOI | 10.3389/fcimb.2021.640561 | |
| Abstract | Leishmania infantum is a protozoan parasite that causes a vector borne infectious disease
in humans known as visceral leishmaniasis (VL). This pathology, also caused by L.
donovani, presently impacts the health of 500,000 people worldwide, and is treated
with outdated anti-parasitic drugs that suffer from poor treatment regimens, severe side
effects, high cost and/or emergence of resistant parasites. In previous works we have
disclosed the anti-Leishmania activity of (-)-Epigallocatechin 3-O-gallate (EGCG), a
flavonoid compound present in green tea leaves. To date, the mechanism of action of
EGCG against Leishmania remains unknown. This work aims to shed new light into the
leishmanicidal mode of action of EGCG. Towards this goal, we first confirmed that EGCG
inhibits L. infantum promastigote proliferation in a concentration-dependent manner.
Second, we established that the leishmanicidal effect of EGCG was associated with i)
mitochondria depolarization and ii) decreased concentration of intracellular ATP, and iii)
increased concentration of intracellular H2O2. Third, we found that the leishmanicidal effect
and the elevated H2O2 levels induced by of EGCG can be abolished by PEG-catalase,
strongly suggesting that this flavonoid kills L. infantum promastigotes by disturbing their
intracellular redox balance. Finally, we gathered in silico and in vitro evidence that EGCG
binds to trypanothione reductase (TR), a central enzyme of the redox homeostasis of
Leishmania, acting as a competitive inhibitor of its trypanothione substrate. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Esquistossomose Experimental. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade do Porto. i3S-Instituto de Investigação e Inovação em Saúde. Porto, Portugal / Universidade do Porto.CBAS-Instituto de Ciências Biomédicas Abel Salazar. Porto, Portugal. | pt_BR |
| Affilliation | Universidade do Porto. i3S-Instituto de Investigação e Inovação em Saúde. Porto, Portugal | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | EGCG | pt_BR |
| Subject | Leishmania infantum | pt_BR |
| Subject | Mechanism of action | pt_BR |
| Subject | Trypanothione reductase | pt_BR |
| Subject | Competitive inhibitor | pt_BR |
