Abstract Number: PB0439
Meeting: ISTH 2021 Congress
Background: Rutin is an anti-inflammatory and anticoagulant flavonoid, which inhibits protein disulfide isomerase (PDI). The venom of the Brazilian pit viper (Bothrops jararaca) is a complex mixture of components, in which snake venom metalloproteinases (SVMP) distinguishes themselves in abundance and high toxicity, and are involved hemostatic disturbances evoked by snakebites. SVMP present procoagulant, proinflammatory, hemorrhagic and lethal activities, and therefore molecules that inhibit these activities are important to improve the treatment of thrombo-hemorrhagic diseases, as snakebite envenomation.
Aims: To investigate the effects of rutin succinate, a water-soluble form of rutin, on coagulation parameters and venom activities, in vitro and in vivo.
Methods: Procedures involving animals were approved by IACUC. The activity of rutin succinate was evaluated on coagulation tests using murine plasma or bovine fibrinogen, on the reducing activity of PDI, and also on proteolytic and coagulant activities of the venom in vitro. In vivo, venom was injected i.p. in C57BL/6 mice alone or pre-incubated with rutin succinate or o-phe (1,10-phenantroline, an SVMP inhibitor) to address the potential of rutin succinate to inhibit the toxic and lethal activities of the venom in vivo.
Results: Rutin succinate prolonged prothrombin time, activated partial thromboplastin time and thrombin time and interacted with PDI and fibrinogen, altering their structures and activities. Rutin succinate was more effective than o-phe to inhibit SVMP, decreasing venom procoagulant activity on plasma or fibrinogen, and venom proteolytic activity on gelatin, casein and fibrinogen. SVMP inhibition by rutin succinate or o-phe completely prevented venom-induced lethality and hemorrhage. Nevertheless, rutin succinate showed a much broader effect, and also improved venom-induced thrombocytopenia and hypofibrinogenemia in mice.
Conclusions: Rutin succinate is a water-soluble compound from rutin, showing anticoagulant and snake venom metalloproteinases-inhibiting properties. It has a great potential as a treatment for snake envenomation, and possibly other thrombo-hemorrhagic diseases.
Funding: FAPESP, CNPq, CAPES, Fundação Butantan.
To cite this abstract in AMA style:Sachetto ATA, Santoro ML. Rutin Succinate Acts as an Anticoagulant and Inhibits Snake Venom Metalloproteinases in an Acute Thrombo-hemorrhagic Disorder Model [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/rutin-succinate-acts-as-an-anticoagulant-and-inhibits-snake-venom-metalloproteinases-in-an-acute-thrombo-hemorrhagic-disorder-model/. Accessed May 20, 2022.
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