Mitochondrial damage contribute to epigallocatechin-3-gallate induced death in Leishmania amazonensis.
Epigallocatechin-3-gallate (EGCG), the most abundant flavonoid in green tea, has been reported to have antiproliferative effects on Trypanosoma cruzi however, the mechanism of protozoan action of EGCG has not been studied. In the present study, we demonstrate the mechanism for the antileishmanial activity of EGCG against Leishmania amazonensis promastigotes. Incubation with EGCG significantly inhibited L. amazonensis promastigote proliferation in a time- and dose-dependent manner. The IC(50) for EGCG at 120 h was 0.063 mM. Ultrastructural alterations of the mitochondria were observed in promastigote treated with EGCG, being the organelle injury reinforced by the decrease in rhodamine 123 fluorescence. The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as Leishmania have been described. The unique mitochondrial features of Leishmania make this organelle an ideal drug target while minimizing toxicity. These data suggest mitochondrial collapse as a part of the EGCG mechanism of action and demonstrate the leishmanicidal effect of EGCG.
Laboratório de Bioquímica de Tripanosomatideos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Job D F
JD
Inacio
Marilene M
MM
Canto-Cavalheiro
Rubem F S
RF
Menna-Barreto
Elmo E
EE
Almeida-Amaral
D000975:Antioxidants / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
D000975:Antioxidants; D000981:Antiprotozoal Agents; D002392:Catechin; C045651:epigallocatechin gallate