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However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. vaginalis<\/jats:named-content>isolates. In this study, we analyzed for the first time the<jats:italic>in vitro<\/jats:italic>effects of the natural polyphenol resveratrol (RESV) on<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. vaginalis<\/jats:named-content>. At concentrations of between 25 and 100 \u03bcM, RESV inhibited the<jats:italic>in vitro<\/jats:italic>growth of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. vaginalis<\/jats:named-content>trophozoites; doses of 25 \u03bcM exerted a cytostatic effect, and higher doses exerted a cytotoxic effect. At these concentrations, RESV caused inhibition of the specific activity of a 120-kDa [Fe]-hydrogenase (Tvhyd). RESV did not affect Tvhyd gene expression and upregulated pyruvate-ferredoxin oxidoreductase (a hydrogenosomal enzyme) gene expression only at a high dose (100 \u03bcM). At doses of 50 to 100 \u03bcM, RESV also caused overexpression of heat shock protein 70 (Hsp70), a protective protein found in the hydrogenosome of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. vaginalis<\/jats:named-content>. The results demonstrate the potential of RESV as an antiparasitic treatment for trichomoniasis and suggest that the mechanism of action involves induction of hydrogenosomal dysfunction. In view of the results, we propose hydrogenosomal metabolism as a key target in the design of novel antiparasitic drugs.<\/jats:p>","DOI":"10.1128\/aac.00009-13","type":"journal-article","created":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T01:07:32Z","timestamp":1363050452000},"page":"2476-2484","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Hydrogenosome Metabolism Is the Key Target for Antiparasitic Activity of Resveratrol against Trichomonas vaginalis"],"prefix":"10.1128","volume":"57","author":[{"given":"Natalia","family":"Mallo","sequence":"first","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Laboratorio de Parasitolog\u00eda, Instituto de Investigaci\u00f3n y An\u00e1lisis Alimentarios, Universidad de Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Lamas","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Ecolog\u00eda, Facultad de Biolog\u00eda, Universidad de Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Leiro","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Laboratorio de Parasitolog\u00eda, Instituto de Investigaci\u00f3n y An\u00e1lisis Alimentarios, Universidad de Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/526497"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.11.1368"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2011.960.966"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2011.02.024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1806.111590"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.783-793.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1258\/0956462053654258"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/647939"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1071\/SH11114"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(95)01347-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/np040106y"},{"key":"e_1_3_2_13_2","first-page":"159","article-title":"Rediscovering natural products as a source of new drugs","volume":"5","author":"Koehn FE","year":"2005","unstructured":"KoehnFE CarterGT. 2005. 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