C5 induces different cell death pathways in promastigotes of Leishmania amazonensis.
Leishmaniasis is a neglected infection that is caused by Leishmania protozoa, affecting millions of people worldwide, mainly in tropical and subtropical regions. This disease has different clinical forms: cutaneous, mucocutaneous, and visceral. The drugs that are currently available for the treatment of this infection have limitations, such as high toxicity, long-term treatment, and leads to drug-resistant strains. Numerous studies, in various experimental models, have sought to develop more effective and less toxic chemotherapeutic agents against leishmaniasis. In the present study, we evaluated the mechanism of cell death that is induced by n-benzyl 1-(4-methoxy)phenyl-9H-β-carboline-3-carboxamide (C5) against Leishmania amazonensis. C5 increased reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, decrease of cell volume, lipoperoxidation, the accumulation of lipid bodies, and acidic vesicular organelles (AVOs) and caused the intense formation of autophagic compartments in L. amazonensis promastigotes. The results indicate that C5 causes L. amazonensis death through different pathways.
Programa de Pós-graduação em Microbiologia, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
Edevi Arbonelli
EA
Mendes
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Vânia Cristina
VC
Desoti
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Sueli de Oliveira
Sde O
Silva
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Tânia
T
Ueda-Nakamura
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Benedito Prado
BP
Dias Filho
Programa de Pós-graduação em Microbiologia, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
Sueli Fumie
SF
Yamada-Ogatta
Departamento de Química, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Maria Helena
MH
Sarragiotto
Programa de Pós-graduação em Microbiologia, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil. Electronic address: cvnakamura@uem.br.
Celso Vataru
CV
Nakamura
D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007894:Leishmania mexicana / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000981:Antiprotozoal Agents; D002243:Carbolines; D017382:Reactive Oxygen Species
Cell death; Leishmania amazonensis; Oxidative damage; β-carboline