Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances
- 1Laboratório de Pesquisa do Biotério Central, Instituto Butantan, São Paulo, Brazil.
- 2Programa de Pós-graduação em Ciências Médicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Abstract
Bites caused by Bothrops snakes represent a major public health problem in South America and are associated with severe systemic and local clinical manifestations. Bothrops venom induces marked hemostatic and inflammatory disturbances that may result in hemorrhage, thrombocytopenia, tissue necrosis, and kidney injury. The recommended treatment for snakebite envenomation is intravenous administration of anti-Bothrops 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 Bothrops jararaca (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 Bothrops venoms. Author summary: When people are bitten by Bothrops snakes, known in Brazil as “jararacas”, the venom causes serious health problems, including bleeding, blood clotting disturbances, and swelling and tissue damage at the site of the bite. The standard treatment is the administration of a specific antivenom produced in horses. However, for people living in remote areas, delays in reaching medical care are common, and antivenom alone is not very effective at reversing the local tissue damage caused by inflammation triggered by the venom. In this study, we explored whether a natural compound called rutin could help reduce the harmful effects of jararaca venom, especially when given in combination with the specific antivenom. Rutin is known for its anti-inflammatory, antioxidant, and blood vessel–protective properties. We tested whether rutin, when given orally, just 10 minutes after venom exposure, could lessen venom-induced damage, either on its own or in combination with antivenom. Our results showed that rutin helped prevent bleeding and tissue death at the venom injection site, reduced inflammation and helped restore blood clotting. Remarkably, these protective effects were observed even when rutin was used without antivenom. These findings suggest that rutin could be a valuable additional treatment for snakebite victims, particularly in situations where access to antivenom is delayed. This research opens new possibilities for supportive treatments, as oral administration of rutin, that help protect patients and reduce injury until full medical care is available.
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BibTeX
@article{oliveira2026rutin,
title = {{Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances}},
author = {Natacha Ferreira de Oliveira and Adrielly Viveiros Torres and Marcelo Larami Santoro},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = oct,
doi = {10.1371/journal.pntd.0014786},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014786},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rutin (quercetin-3-rutinoside) administered orally after experimental Bothrops jararaca envenomation prevents hemostatic, inflammatory and hemorrhagic disturbances
AU - Natacha Ferreira de Oliveira
AU - Adrielly Viveiros Torres
AU - Marcelo Larami Santoro
PY - 2026
DA - 2026/10/06
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014786
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014786
AB - Bites caused by Bothrops snakes represent a major public health problem in South America and are associated with severe systemic and local clinical manifestations. Bothrops venom induces marked hemostatic and inflammatory disturbances that may result in hemorrhage, thrombocytopenia, tissue necrosis, and kidney injury. The recommended treatment for snakebite envenomation is intravenous administration of anti-Bothrops 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 Bothrops jararaca (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 Bothrops venoms. Author summary: When people are bitten by Bothrops snakes, known in Brazil as “jararacas”, the venom causes serious health problems, including bleeding, blood clotting disturbances, and swelling and tissue damage at the site of the bite. The standard treatment is the administration of a specific antivenom produced in horses. However, for people living in remote areas, delays in reaching medical care are common, and antivenom alone is not very effective at reversing the local tissue damage caused by inflammation triggered by the venom. In this study, we explored whether a natural compound called rutin could help reduce the harmful effects of jararaca venom, especially when given in combination with the specific antivenom. Rutin is known for its anti-inflammatory, antioxidant, and blood vessel–protective properties. We tested whether rutin, when given orally, just 10 minutes after venom exposure, could lessen venom-induced damage, either on its own or in combination with antivenom. Our results showed that rutin helped prevent bleeding and tissue death at the venom injection site, reduced inflammation and helped restore blood clotting. Remarkably, these protective effects were observed even when rutin was used without antivenom. These findings suggest that rutin could be a valuable additional treatment for snakebite victims, particularly in situations where access to antivenom is delayed. This research opens new possibilities for supportive treatments, as oral administration of rutin, that help protect patients and reduce injury until full medical care is available.
SN - 1935-2735
SN - 1935-2727
ER -