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Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target.
Argüello-García, Raúl; Calzada, Fernando; García-Hernández, Normand; Chávez-Munguía, Bibiana; Velázquez-Domínguez, José Antonio.
Afiliação
  • Argüello-García R; Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional, Departamento de Genética y Biología Molecular, Ciudad de México, México.
  • Calzada F; Centro Médico Nacional Siglo XXI, Unidad Médica de Alta Especialidad, Unidad de Investigación Médica en Farmacología, Ciudad de México, México.
  • García-Hernández N; Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Unidad Médica de Alta Especialidad, Hospital de Pediatría, Unidad de Investigación Médica en Genética Humana, Ciudad de México, México.
  • Chávez-Munguía B; Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Ciudad de México, México.
  • Velázquez-Domínguez JA; Instituto Politécnico Nacional, Escuela Nacional de Medicina y Homeopatía, Ciudad de México, México.
Mem Inst Oswaldo Cruz ; 115: e200127, 2020.
Article em En | MEDLINE | ID: mdl-33111756
BACKGROUND: Kaempferol (KPF) is a flavonoid with antiparasitic activity including experimental giardiasis which mechanism of action is unknown. OBJECTIVE: To analyse the cytotoxic effects of KPF on Giardia duodenalis trophozoites and to identify a likely parasite target of this compound. METHODS: We used inhibitory concentrations of KPF (IC25, IC50 and IC100) and albendazole (ABZ) as reference drug. The ultrastructure of the trophozoites was analysed by transmission electron microscopy (TEM) whilst apoptosis/necrosis, production of reactive oxygen species (ROS) and cell cycle progression were assessed by flow cytometry (FCM) and confocal laser microscopy (CLM). Ligand-protein docking analyses were carried out using KPF structure from a drug library and crystal structure of a G. duodenalis aldose reductase (GdAldRed) homolog. RESULTS: KPF provoked appearance of perinuclear and periplasmic spaces devoid of cytosolic content and multilamellar structures. KPF induced proapoptotic death associated with partial arrest in the S phase without ROS production. Bioinformatics approaches predicted that GdAldRed is a viable KPF target (ΔG = -7.09 kCal/mol), exhibiting 92% structural identity and a similar coupling pattern as its human homolog. CONCLUSIONS: KPF exerted a proapoptotic effect on G. duodenalis trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures. GdAldRed is a likely target underlying its antigiardial activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Giardíase / Giardia lamblia / Quempferóis Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mem Inst Oswaldo Cruz Ano de publicação: 2020 Tipo de documento: Article País de publicação: Brasil
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Giardíase / Giardia lamblia / Quempferóis Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mem Inst Oswaldo Cruz Ano de publicação: 2020 Tipo de documento: Article País de publicação: Brasil