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Diseases","award":["INCT-DT-465229\/2014-0"],"award-info":[{"award-number":["INCT-DT-465229\/2014-0"]}]},{"name":"CAPES","award":["CNPq 305235\/2019-2"],"award-info":[{"award-number":["CNPq 305235\/2019-2"]}]},{"name":"CAPES","award":["CNPq 309901\/2023-5"],"award-info":[{"award-number":["CNPq 309901\/2023-5"]}]},{"name":"CAPES","award":["FAPESB\/PPSUS 5186"],"award-info":[{"award-number":["FAPESB\/PPSUS 5186"]}]},{"name":"CAPES","award":["46700287000"],"award-info":[{"award-number":["46700287000"]}]},{"name":"CAPES","award":["INCT-DT-465229\/2014-0"],"award-info":[{"award-number":["INCT-DT-465229\/2014-0"]}]},{"name":"PDJ Inova Fiocruz","award":["CNPq 305235\/2019-2"],"award-info":[{"award-number":["CNPq 305235\/2019-2"]}]},{"name":"PDJ Inova Fiocruz","award":["CNPq 309901\/2023-5"],"award-info":[{"award-number":["CNPq 309901\/2023-5"]}]},{"name":"PDJ Inova Fiocruz","award":["FAPESB\/PPSUS 5186"],"award-info":[{"award-number":["FAPESB\/PPSUS 5186"]}]},{"name":"PDJ Inova Fiocruz","award":["46700287000"],"award-info":[{"award-number":["46700287000"]}]},{"name":"PDJ Inova Fiocruz","award":["INCT-DT-465229\/2014-0"],"award-info":[{"award-number":["INCT-DT-465229\/2014-0"]}]},{"name":"Fiotec\u2014Fiocruz","award":["CNPq 305235\/2019-2"],"award-info":[{"award-number":["CNPq 305235\/2019-2"]}]},{"name":"Fiotec\u2014Fiocruz","award":["CNPq 309901\/2023-5"],"award-info":[{"award-number":["CNPq 309901\/2023-5"]}]},{"name":"Fiotec\u2014Fiocruz","award":["FAPESB\/PPSUS 5186"],"award-info":[{"award-number":["FAPESB\/PPSUS 5186"]}]},{"name":"Fiotec\u2014Fiocruz","award":["46700287000"],"award-info":[{"award-number":["46700287000"]}]},{"name":"Fiotec\u2014Fiocruz","award":["INCT-DT-465229\/2014-0"],"award-info":[{"award-number":["INCT-DT-465229\/2014-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB\/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG\u2019s cytotoxic effect on bone marrow-derived macrophages (BMM\u03a6) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound\u2019s efficacy in BALB\/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-\u03b3, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusions: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.<\/jats:p>","DOI":"10.3390\/pathogens13080630","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T12:27:43Z","timestamp":1722256063000},"page":"630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Leishmania braziliensis Infection in BALB\/c Mice: A Preclinical Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-2916","authenticated-orcid":false,"given":"Kercia P.","family":"Cruz","sequence":"first","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio L. O. A.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"},{"name":"Baiano Federal Institute of Education, Science and Technology\u2014Santa In\u00eas Campus, BR 420, Santa In\u00eas Road, Rural Zone, Uba\u00edra 45320-000, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina F.","family":"Amorim","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-3861","authenticated-orcid":false,"given":"Alan G. S. F.","family":"Pinho","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana C.","family":"Palma","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana A. S.","family":"Dantas","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana R. G.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine S. A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0683-9111","authenticated-orcid":false,"given":"Ana Luiza J.","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabella G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella B.","family":"Pita","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca C. A.","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Structural and Molecular Pathology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto C.","family":"Bomfim","sequence":"additional","affiliation":[{"name":"Laboratory of Population Genetics and Molecular Evolution, Biology Institute, Federal University of Bahia, Salvador 40170-110, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udia I.","family":"Brodskyn","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-0319","authenticated-orcid":false,"given":"Deborah B. M.","family":"Fraga","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Preventive Veterinary Medicine and Animal Production, School of Veterinary Medicine and Animal Science, Federal University of Bahia, Salvador 40170-110, Bahia, Brazil"},{"name":"National Institute of Science and Technology of Tropical Diseases (INCT-DT), National Council for Scientific Research and Development (CNPq)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5325-5299","authenticated-orcid":false,"given":"Isadora S.","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Structural and Molecular Pathology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria B. R.","family":"de_Santana","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena M. P.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9380-8839","authenticated-orcid":false,"given":"Juliana P. B.","family":"de_Menezes","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Parasite Interaction and Epidemiology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5075-1254","authenticated-orcid":false,"given":"Washington L. C.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Structural and Molecular Pathology, Gon\u00e7alo Moniz Institute, Fiocruz-Bahia, Salvador 40296-710, Bahia, Brazil"},{"name":"Department of Pathology and Forensic Medicine, Bahia Medical School, Federal University of Bahia, Salvador 40110-906, Bahia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-9263","authenticated-orcid":false,"given":"Patr\u00edcia S. 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