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https://www.arca.fiocruz.br/handle/icict/11992
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- IOC - Artigos de Periódicos [12488]
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EFFECT OF APIGENIN ON LEISHMANIA AMAZONENSIS IS ASSOCIATED WITH REACTIVE OXYGEN SPECIES PRODUCTION FOLLOWED BY MITOCHONDRIAL DYSFUNCTION
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Resumo em Inglês
Leishmaniasis is an important neglected disease caused by protozoa of the genus
Leishmania that affects more than 12 million people worldwide. Leishmaniasis treatment
requires the administration of toxic and poorly tolerated drugs, and parasite resistance greatly
reduces the efficacy of conventional medications. Apigenin (1), a naturally occurring plant
flavone, has a wide range of reported biological effects. In this study, antileishmanial activity of 1
in vitro was investigated, and its mechanism of action against Leishmania amazonensis
promastigotes was described. Treatment with 1 for 24 h resulted in concentration-dependent
inhibition of cellular proliferation (IC50 = 23.7 μM) and increased reactive oxygen species
(ROS) generation. Glutathione and N-acetyl-L-cysteine protected L. amazonensis from the
effects of 1 and reduced ROS levels after the treatment. By contrast, oxidized glutathione did
not reduce the levels of ROS caused by 1 by not preventing the proliferation inhibition.
Apigenin 1 also induced an extensive swelling in parasite mitochondria, leading to an alteration
of the mitochondrial membrane potential, rupture of the trans-Golgi network, and cytoplasmic
vacuolization. These results demonstrate the leishmanicidal effect of 1 and suggest the
involvement of ROS leading to mitochondrial collapse as part of the mechanism of action.
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