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Therefore, the aim of this study was to evaluate ZnO nanocrystals and Ag-ZnO\/AgO nanocomposites containing different proportions of silver (ZnO:5Ag, ZnO:9Ag and ZnO:11Ag) in an experimental model of the acute phase of CD. Methods: C57Bl\/6 mice were infected with 1000 forms of the Colombian strain of T. cruzi. The treatment was carried out by gavage with 5 mg\/kg\/d for 7 consecutive days from the first detection of parasitemia. Weight, parasitemia and survival were assessed during treatment and up to the day of euthanasia. After euthanasia, the cardiac and intestinal parasitism, inflammatory infiltrate, collagen deposition and cytokine dosages were analyzed. Results: It was observed that the nanocomposites ZnO:9Ag and ZnO:11Ag were the most effective in reducing parasitemia and increasing the survival of the infected animals. However, pure ZnO induced the maintenance of parasitemia and reduced their survival. The ZnO:9Ag and ZnO:11Ag nanocomposites were able to reduce the number of cardiac amastigote nests. In addition, they were responsible for reducing TNF-\u03b1 and IL-6 in situ. ZnO:9Ag and ZnO:11Ag induced a reduction in the intestinal inflammatory infiltrate and neuronal protection in the myenteric plexus, as well as reducing TNF-\u03b1 in situ. Conclusions: Based on these results, it is suggested that there is an ideal concentration in terms of the proportion of Ag\/AgO and ZnO in nanocomposites for use against CD. Thus, ZnO:9Ag or ZnO:11Ag nanomaterials are potential candidates for the development of new biotechnological products for the therapy of CD.<\/jats:p>","DOI":"10.3390\/pharmaceutics16111415","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T09:52:54Z","timestamp":1730713974000},"page":"1415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Achieving the Optimal AgO Concentrations to Modulate the Anti-Trypanosoma cruzi Activity of Ag-ZnO\/AgO Nanocomposites: In Vivo Investigations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-5112","authenticated-orcid":false,"given":"Jos\u00e9 Rodrigues","family":"do Carmo Neto","sequence":"first","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarlla Loyane Lira","family":"Braga","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-1050","authenticated-orcid":false,"given":"Pablo Igor Ribeiro","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordana Fernandes","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-9142","authenticated-orcid":false,"given":"Rafael Obata","family":"Trevisan","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Federal University of Tri\u00e2ngulo Mineiro, Uberaba 38025-180, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8482-5713","authenticated-orcid":false,"given":"Karen Martins","family":"Mendes","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Federal University of Tri\u00e2ngulo Mineiro, Uberaba 38025-180, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-6751","authenticated-orcid":false,"given":"Milton Adriano Pelli","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-007X","authenticated-orcid":false,"given":"Mara R\u00fabia Nunes","family":"Celes","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-156X","authenticated-orcid":false,"given":"Anielle Christine Almeida","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Novos Materiais Nanoestruturados e Funcionais (LNMIS), Physics Institute, Federal University of Alagoas, Macei\u00f3 57072-900, AL, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Reis","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goi\u00e2nia 74605-050, GO, Brazil"},{"name":"Department of General Pathology, Federal University of Tri\u00e2ngulo Mineiro, Uberaba 38025-180, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-7621","authenticated-orcid":false,"given":"Marcos Vin\u00edcius","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences of Federal University of Tri\u00e2ngulo Mineiro, Uberaba 38025-180, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chao, C., Leone, J.L., and Vigliano, C.A. 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