{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T14:16:08Z","timestamp":1777299368293,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T00:00:00Z","timestamp":1578528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Healthy and the National Council for Scientific and Technological Development","award":["403006\/2016-3"],"award-info":[{"award-number":["403006\/2016-3"]}]},{"name":"Ministry of Healthy and the National Council for Scientific and Technological Development","award":["440010\/2018-7"],"award-info":[{"award-number":["440010\/2018-7"]}]},{"name":"Ministry of Healthy and the National Council for Scientific and Technological Development","award":["302670\/2017-3"],"award-info":[{"award-number":["302670\/2017-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC\u00a0+\u00a0AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC\u00a0+\u00a0AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3\u00a0hours and reduced levels after 24\u00a0hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC\u00a0+\u00a0AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC\u00a0+\u00a0AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC\u00a0+\u00a0AMB may represent an alternative adjuvant for the treatment of cryptococcosis.<\/jats:p>","DOI":"10.1093\/mmy\/myz129","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T20:10:06Z","timestamp":1576095006000},"page":"835-844","source":"Crossref","is-referenced-by-count":6,"title":["N-acetylcysteine reduces amphotericin B deoxycholate nephrotoxicity and improves the outcome of murine cryptococcosis"],"prefix":"10.1093","volume":"58","author":[{"given":"Thais Furtado Ferreira","family":"Magalh\u00e3es","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marliete Carvalho","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, 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