Snakebite envenomation is a neglected tropical disease that affects between 4.5 and 5.4 million people annually. In South America, snakes of the Bothrops genus are the main medically relevant species involved in envenomations. Bothrops venom, rich in hemotoxic enzymes and toxins, frequently induces thrombocytopenia. Although it is known that venom toxins activate and remove platelets from circulation, the underlying mechanisms remain unclear. One proposed mechanism is platelet desialylation, induced by neuraminidases, which remove sialic acid from the platelet surface, promoting their clearance from circulation. Oseltamivir phosphate (Tamiflu®), an antiviral used against Influenza, inhibits viral neuraminidases and has been suggested as an adjuvant to block endogenous neuraminidase activity, potentially extending platelet lifespan.
This study investigated the effects of oseltamivir phosphate on thrombocytopenia induced by Bothrops jararaca venom (BjV) in Swiss mice (IACUC Instituto Butantan, protocol no. 7416200723). Animals were divided into four groups, receiving intraperitoneal injections of saline (SAL) or oseltamivir phosphate (OSELT), followed by subcutaneous administration of SAL or BjV. Blood samples were collected 3 and 6 hours after envenomation, and hematological parameters were analyzed using an automated cell counter. Data was assessed using one-way ANOVA and post hoc tests.
Envenomed groups exhibited significant thrombocytopenia, which was not reversed by oseltamivir. In healthy animals, the drug did not alter platelet levels. Lymphocytopenia was observed in BjV-treated groups, along with an increase in leukocyte count, including a mild elevation in the OSELT+SAL group. Red blood cell counts and hematocrit levels remained stable.
In conclusion, exposure to BjV led to thrombocytopenia, lymphocytopenia, and leukocytosis—all of which were not reversed by Oseltamivir treatment. While the drug appeared neutral in healthy animals, it was not effective in preventing the acute hematological effects of the venom when administered in isolation.