{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:43:56Z","timestamp":1788903836649,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407768\/2013-0"],"award-info":[{"award-number":["407768\/2013-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.200554\/2018-00"],"award-info":[{"award-number":["88887.200554\/2018-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Hydroethanolic preparations of the botanical species Acmella oleracea L. are used in the north of Brazil for the treatment of various diseases. However, few studies have been conducted to evaluate the toxicity of this species. The objective of this study was to evaluate the acute toxicity of the hydroethanolic extract of A. oleracea L. (EHFAo) flowers in zebrafish by immersion and oral administration. The extract was analyzed by ultra-performance liquid chromatography\u2013mass spectrometry (UPLC\u2013MS). EHFAo was administered orally (44.457, 88.915, 199.94, 281.83, and 448.81 mg\/kg) and by immersion (250, 300, 350, 400, and 450 \u00b5g\/L). Behavioral and histopathological analysis of gills, liver, intestine, and kidney were performed. The presence of (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol) in EHFAo was identified by ultra-high-re.solution liquid chromatography\u2013electrospray ionization mass spectrometry (UHPLC\u2013ESI-MS). Treatment with EHFAo caused significant behavioral changes and death. The calculated median lethal dose (LD50) was 148.42 mg\/kg, and the calculated median lethal concentration (LC50) was 320 \u03bcg\/L. In the histopathological study, it was observed that upon oral treatment, the tissue alterations that compromised the normal functioning of the organism occurred with EHFAo doses of 88.915, 199.53, and 281.83 mg\/kg, the intestine being the most affected. When the treatment was performed by immersion, the most toxic EHFAo concentrations according to the histopathological evaluation were 300, 350, and 400 \u03bcg\/L, with the most affected organ being the gills. Finally, EHFAo in this study was shown to be more toxic to the liver, intestine, and kidneys when administered orally and to gills, liver, and kidneys when administered by immersion in water. Therefore, considering the results obtained and the chemical characteristics of the main phytochemical marker of EHFAo, spilanthol, it can be suggested that, depending on the dose, this compound can lead to histopathological damages in the organs highlighted in this study.<\/jats:p>","DOI":"10.3390\/ph12040173","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T11:07:00Z","timestamp":1574852820000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Acute Toxicity of the Hydroethanolic Extract of the Flowers of Acmella oleracea L. in Zebrafish (Danio rerio): Behavioral and Histopathological Studies"],"prefix":"10.3390","volume":"12","author":[{"given":"Gisele","family":"Custodio de Souza","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Farmac\u00eautica, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farmacia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"},{"name":"Laborat\u00f3rio de Pesquisa em F\u00e1rmacos, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ianna","family":"Dias Ribeiro da Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muller","family":"Duarte Viana","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em F\u00e1rmacos, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-9460","authenticated-orcid":false,"given":"Nayara","family":"Costa de Melo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em F\u00e1rmacos, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"S\u00e1nchez-Ortiz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em F\u00e1rmacos, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monaliza","family":"Maia Rebelo de Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-8245","authenticated-orcid":false,"given":"Wagner","family":"Ramos Barbosa","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-0105","authenticated-orcid":false,"given":"Irlon","family":"Maciel Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biocat\u00e1lise e S\u00edntese Org\u00e2nica Aplicada, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-9794","authenticated-orcid":false,"given":"Jos\u00e9","family":"Tavares Carvalho","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Farmac\u00eautica, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farmacia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"},{"name":"Laborat\u00f3rio de Pesquisa em F\u00e1rmacos, Departamento de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Colegiado de Farm\u00e1cia, Universidade Federal do Amap\u00e1, Macap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.aquatox.2005.09.009","article-title":"Ecotoxicology of human pharmaceuticals","volume":"76","author":"Fent","year":"2006","journal-title":"Aquat. 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