Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target
Mem. Inst. Oswaldo Cruz
; 115: e200127, 2020. graf
Article
in English
| LILACS, Sec. Est. Saúde SP
| ID: biblio-1135244
Responsible library:
BR1.1
ABSTRACT
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.
Full text:
Available
Collection:
National databases
/
Brazil
Health context:
SDG3 - Health and Well-Being
Health problem:
Target 3.3: End transmission of communicable diseases
Database:
LILACS
/
Sec. Est. Saúde SP
Main subject:
Giardiasis
/
Giardia lamblia
/
Kaempferols
Type of study:
Prognostic study
/
Risk factors
Limits:
Animals
/
Humans
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Year:
2020
Document type:
Article
Institution/Affiliation country:
Centro Médico Nacional Siglo XXI/MX
/
Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional/MX
/
Instituto Mexicano del Seguro Social/MX