Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants.

Autor: Teixeira SC; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Paschoalino M; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., de Souza G; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Rosini AM; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., de Lima Junior JP; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Luz LC; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Fajardo Martínez AF; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Alves RN; Department of Agricultural and Natural Sciences, Universidade do Estado de Minas Gerais, Ituiutaba, MG, Brazil., Almeida MPO; Laboratory of Immunopathology, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Damasceno JL; Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Silva MJB; Department of Immunology, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Ietta F; Department of Life Sciences, University of Siena, Siena, Italy., Barbosa BF; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Ferro EAV; Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil. Electronic address: eloisa.ferro@ufu.br., Gomes Martins CH; Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil. Electronic address: carlos.martins2@ufu.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2023 Oct 01; Vol. 384, pp. 110716. Date of Electronic Publication: 2023 Sep 16.
DOI: 10.1016/j.cbi.2023.110716
Abstrakt: Congenital toxoplasmosis, caused by the opportunistic protozoan parasite T. gondii, can cause stillbirths, miscarriages and fetal abnormalities, as well as encephalitis and chorioretinitis in newborns. Available treatment options rely on antiparasitic drugs that have been linked to serious side effects, high toxicity and the development of drug-resistant parasites. The search for alternative therapeutics to treat this disease without acute toxicity for the mother and child is essential for the advancement of current therapeutic procedures. The present study aimed to unravel the mode of the anti-T. gondii action of Rottlerin, a natural polyphenol with multiple pharmacological properties described. Herein, we further assessed the antiparasitic activity of Rottlerin against T. gondii infection on the human trophoblastic cells (BeWo cells) and, for the first time, on human villous explants. We found that non-cytotoxic doses of Rottlerin impaired early and late steps of parasite infection with an irreversible manner in BeWo cells. Rottlerin caused parasite cell cycle arrest in G1 phase and compromised the ability of tachyzoites to infect new cells, thus highlighting the possible direct action on parasites. An additional and non-exclusive mechanism of action of Rottlerin involves the modulation of host cell components, by affecting lipid droplet formation, mitochondrial function and upregulation of the IL-6 and MIF levels in BeWo cells. Supporting our findings, Rottlerin also controlled T. gondii proliferation in villous explants with low toxicity and reduced the IL-10 levels, a cytokine associated with parasite susceptibility. Collectively, our results highlighted the potential use of Rottlerin as a promising tool to prevent and/or treat congenital toxoplasmosis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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