Oral Rutin Reduces the Hemostatic Impairment Induced by Bothrops jararaca Venom in Experimental Models

Introduction: Bothrops jararaca (Bj) snakebites cause hemostatic and inflammatory disturbances in victims. Bj venom contains various proteins that induce local and systemic bleeding, thrombocytopenia, and consumption coagulopathy. Parenteral administration of rutin, a bioflavonoid, has shown potential in mitigating venom effects by reducing bleeding time, delaying coagulopathy, and decreasing local hemorrhage (doi: 10.3389/fphar.2022.828269), and thereby may accelerate the recovery of patients treated with specific antivenom therapy (SAB).

Aims: To evaluate the potential use of orally administered nano-rutin in reducing the hemorrhagic effects and hemostatic disturbances caused by Bj envenomation. Additionally, this study aimed to explore the role of cfDNA in the pathophysiology of envenomation and assess the levels of inflammatory markers in animals treated with a combination of nano-rutin and SAB.

Methods: The use of male C57BL/6 mice was approved by IACUC (4491070319). Mice were divided into experimental groups (n=10/group) and evaluated at 6 and 12h after s.c. administration of saline or Bj venom. Nano-rutin (v.o.) and/or SAB therapy (i.v.) were administered following venom administration.

Results: Marked hypofibrinogenemia, increased IL-6 levels, and intense local hemorrhage were observed in envenomed mice. The association of nano-rutin with SAB restored fibrinogen and IL-6 levels faster than SAB or rutin alone. This association also blocked the development of local hemorrhage. Nano-rutin alone increased NO levels. The levels of cfDNA were not significantly different from those of the controls, but were higher with this association at 6h.

Conclusions: The association of the administration of nano-rutin followed by SAB enhanced the recovery of inflammatory and hemostatic markers after Bj envenomation, representing a promising strategy for snakebite treatment.
Acknowledgements: CAPES (#88887.886144/2023-00), Fundação Butantan, and (CNPq, # 309980/2021-6).