{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:16:23Z","timestamp":1792696583984,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"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\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Brazilian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:label\/>\n                  <jats:p>Onychomycosis is a nail infection caused by Trichophyton interdigitale and other fungi, which can be treated with topical amorolfine (AMR) and ciclopirox olamine (CPX). Although these drugs are widely used, little is known about the role of reactive oxygen (ROS) and nitrogen (RNS) in their mechanism of action. To better understand the effects of AMR and CPX in dermatophytes, we evaluated whether they act through the production of ROS and peroxynitrite (PRN). We tested a set of strains, all susceptible to AMR and CPX, and these antifungals significantly reduced T. interdigitale viability within 24 h. This effect occurred concomitantly with reduced ergosterol, increased production of ROS and PRN, and consequently increased lipid peroxidation. Together, these mechanisms lead to cell damage and fungal death. These fungicidal effects were abolished when PRN and superoxide scavengers were used in the assays, demonstrating the role of these species in the mechanism of action. We also studied the antioxidant system when T. interdigitale was exposed to AMR and CPX. Interestingly, superoxide dismutase and catalase inhibition lead to altered ROS and PRN production, lipid peroxidation, and ergosterol levels. In fact, the combination of AMR or CPX with a superoxide dismutase inhibitor was antagonistic. Together, these data demonstrate the importance of ROS and PRN in the antifungal action of AMR and CPX against the evaluated T. interdigitale strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Onychomycosis is a nail infection, which can be treated with amorolfine and ciclopirox olamine. Here we demonstrate that these drugs exhibit antifungal activity also through the production of oxidative and nitrosative radicals.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mmy\/myac058","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T02:19:59Z","timestamp":1658974799000},"source":"Crossref","is-referenced-by-count":13,"title":["Reactive oxygen and nitrogen species are crucial for the antifungal activity of amorolfine and ciclopirox olamine against the dermatophyte <i>Trichophyton interdigitale<\/i>"],"prefix":"10.1093","volume":"60","author":[{"given":"Paulo H F","family":"Carmo","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo J C","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o C M","family":"Dornelas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna C T","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila M","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella F","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Programa Multic\u00eantrico de P\u00f3s Gradua\u00e7\u00e3o em Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Juiz de Fora , Rua S\u00e3o Paulo, 745, Centro, 35010-180, Governador Valadares, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalu T A","family":"Peres","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-5666","authenticated-orcid":false,"given":"Daniel A","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"2022081811583905500_bib1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.7547\/0003-0538-104.4.330","article-title":"Molecular determination of mixed infections of dermatophytes and nondermatophyte molds in 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