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The recommended treatment for snakebite envenomation is intravenous administration of anti-\n                    <jats:italic>Bothrops<\/jats:italic>\n                    antivenom (SAB); however, this therapy has limited efficacy against venom-induced local tissue injury mediated by the release of inflammatory mediators. In this context, adjunct pharmacological strategies capable of delaying or attenuating envenomation effects before antivenom administration may be clinically valuable, particularly in remote settings. Rutin and its derivative, rutin succinate, are flavonoids with anti-inflammatory, antioxidant, and vasoprotective properties, and have been previously shown to mitigate venom-induced damage when administered parenterally prior to\n                    <jats:italic>Bothrops jararaca<\/jats:italic>\n                    (Bj) envenomation. Herein, we evaluated the efficacy of orally administered rutin, formulated for rapid gastrointestinal absorption (nano-rutin), used alone or in combination with SAB, in a murine model of Bj snakebite envenomation. Mice received nano-rutin by gavage 10 min after venom injection and were subsequently treated with or without SAB after 1 hour. Envenomed mice developed thrombocytopenia, leukocytosis, fibrinogen consumption, elevated levels of IL-6 and cell-free DNA (cfDNA), reduced DNAse activity, hypoalbuminemia, and marked local hemorrhage and dermonecrosis. Oral nano-rutin restored most evaluated systemic parameters, and significantly reduced local hemorrhage and dermonecrosis, even in the absence of SAB. These findings support nano-rutin as an effective complementary therapy to antivenom, particularly for mitigating local tissue damage induced by\n                    <jats:italic>Bothrops<\/jats:italic>\n                    venoms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014786","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:45:23Z","timestamp":1791308723000},"page":"e0014786","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances"],"prefix":"10.1371","volume":"20","author":[{"given":"Natacha Ferreira","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Biot\u00e9rio Central, Instituto Butantan","place":["S\u00e3o Paulo, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias M\u00e9dicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrielly Viveiros","family":"Torres","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Biot\u00e9rio Central, Instituto Butantan","place":["S\u00e3o Paulo, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias M\u00e9dicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-3757","authenticated-orcid":true,"given":"Marcelo Larami","family":"Santoro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa do Biot\u00e9rio Central, Instituto Butantan","place":["S\u00e3o Paulo, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias M\u00e9dicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"pntd.0014786.ref001"},{"issue":"6","key":"pntd.0014786.ref002","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1590\/S0037-86821997000600006","article-title":"Acidente por serpentes do g\u00eanero Bothrops: S\u00e9rie de 3.139 casos","volume":"30","author":"LA Ribeiro","year":"1997","journal-title":"Rev Soc Bras Med Trop"},{"key":"pntd.0014786.ref003","article-title":"What are the characteristics and where is the highest risk of snakebite accidents in the state of S\u00e3o Paulo?","volume":"28","author":"GD de Freitas","year":"2025","journal-title":"Rev Bras Epidemiol"},{"key":"pntd.0014786.ref004","first-page":"81","article-title":"Acidente botr\u00f3pico.","volume-title":"Animais pe\u00e7onhentos no Brasil","author":"FOS Fran\u00e7a","year":"2009","edition":"2"},{"issue":"3","key":"pntd.0014786.ref005","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/15563650.2018.1510129","article-title":"Acute kidney injury induced by thrombotic microangiopathy in two cases of Bothrops envenomation","volume":"57","author":"CMS Malaque","year":"2019","journal-title":"Clin Toxicol (Phila)"},{"issue":"7","key":"pntd.0014786.ref006","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.toxicon.2009.07.001","article-title":"Epidemiological, clinical and therapeutic aspects of Bothrops asper bites","volume":"54","author":"R Otero-Pati\u00f1o","year":"2009","journal-title":"Toxicon"},{"key":"pntd.0014786.ref007","article-title":"Acute compartment syndrome in Bothrops atrox envenomation: A case-control study in the Brazilian Amazon","volume":"32","author":"G de OB do Nascimento","year":"2026","journal-title":"J Venom Anim Toxins Incl Trop Dis"},{"key":"pntd.0014786.ref008","doi-asserted-by":"crossref","first-page":"107350","DOI":"10.1016\/j.toxicon.2023.107350","article-title":"Hemoperitoneum after a Bothrops snakebite: Case report","volume":"237","author":"AB Abad Ribeiro","year":"2024","journal-title":"Toxicon"},{"key":"pntd.0014786.ref009","doi-asserted-by":"crossref","first-page":"107682","DOI":"10.1016\/j.toxicon.2024.107682","article-title":"Long-term hospital care needs after Bothrops atrox envenomation with hemorrhagic stroke in the Brazilian Amazon: \u201cFrom social to physical death\u201d - 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