{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:59:45Z","timestamp":1791575985516,"version":"4.3.4"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidade Federal de Uberl\u00e2ndia (UFU)"},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais (FAPEMIG)"},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A2 (PLA2) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 \u00b5g\/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor\u2014potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 \u03bcg\/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal\u2013fetal interface.<\/jats:p>","DOI":"10.3390\/ph18091260","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:57Z","timestamp":1756189557000},"page":"1260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["BthTX-II, an Asp49 PLA2 from Bothrops jararacussu, Impairs Toxoplasma gondii Infection: In Vitro and Ex Vivo Approaches"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-7113","authenticated-orcid":false,"given":"Vin\u00edcius Queiroz","family":"Oliveira","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4425-1867","authenticated-orcid":false,"given":"Emanuelle Lorrayne","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Pinheiro","family":"Morais","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8676-630X","authenticated-orcid":false,"given":"Leonardo Alves","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel de Oliveira","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-1925","authenticated-orcid":false,"given":"Marcos Paulo Oliveira","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joed Pires de Lima","family":"J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia Carine Lima","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-9172","authenticated-orcid":false,"given":"Rafael Martins","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e1ssia Rafaela","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Proteins and Bioactive Compounds in the Western Amazon (LABIOPROT), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ Rond\u00f4nia), Universidade Federal de Rond\u00f4nia (UNIR), National Institute of Science and Technology of Epidemiology of the Western Amazon, INCT-EPIAMO, Porto Velho 76812-245, RO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreimar Martins","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Proteins and Bioactive Compounds in the Western Amazon (LABIOPROT), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ Rond\u00f4nia), Universidade Federal de Rond\u00f4nia (UNIR), National Institute of Science and Technology of Epidemiology of the Western Amazon, INCT-EPIAMO, Porto Velho 76812-245, RO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa Carregosa","family":"Santos","sequence":"additional","affiliation":[{"name":"Institute Multidisciplinary in Health, Universidade Federal da Bahia, Vit\u00f3ria da Conquista 45029-094, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiana Silva","family":"Lopes","sequence":"additional","affiliation":[{"name":"Institute Multidisciplinary in Health, Universidade Federal da Bahia, Vit\u00f3ria da Conquista 45029-094, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-5162","authenticated-orcid":false,"given":"Emidio","family":"Beraldo-Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica Oliveira","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Interactions, Institute of Natural and Biological Sciences, Universidade Federal do Tri\u00e2ngulo Mineiro, Uberaba 38025-350, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovita Eug\u00eania Gazzinelli Cruz","family":"Madeira","sequence":"additional","affiliation":[{"name":"Laboratory of Micotoxins, Funda\u00e7\u00e3o Ezequiel Dias, Belo Horizonte 30510-010, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-2844","authenticated-orcid":false,"given":"Bellisa Freitas","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-2583","authenticated-orcid":false,"given":"Eloisa Am\u00e1lia Vieira","family":"Ferro","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Cota","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-9197","authenticated-orcid":false,"given":"Veridiana de Melo Rodrigues","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Universidade Federal de Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1017\/S0031182021001013","article-title":"Congenital Toxoplasmosis in Humans: An Update of Worldwide Rate of Congenital Infections","volume":"148","author":"Dubey","year":"2021","journal-title":"Parasitology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Flegr, J., Prandota, J., Sovi\u010dkov\u00e1, M., and Israili, Z.H. 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