Phenolic acids inhibit local and systemic effects induced by Bothrops brazili venom

Bothropic envenomation induces local damage, such as edema, necrosis, and hemorrhage, as well as systemic effects, including cardiovascular, renal and coagulation disturbances. While serum therapy remains, the primary treatment used for snakebites and efficiently neutralizes systemic damage, it inadequately addresses local tissue injury. Aiming to understand the pathophysiological mechanism of Bothrops brazili envenomation and explore novel complementary treatments, this study evaluated the local and systemic injuries caused by B. brazili venom and their mitigation by chlorogenic and rosmarinic acids. The venom exhibited high proteolytic and phospholipase activities, caused inflammation with edema formation, increased myeloperoxidase and cytokine dosage (IL-1β and IL-6). These effects were attenuated by phenolic acids. Molecular docking analysis assessed the interaction of these acids with B. brazili venom toxins, specifically catalytic PLA₂ (BbTX-III) and non-catalytic Lys49-PLA₂ (MTX-II). Chlorogenic and rosmarinic acids showed superior binding energies with MTX-II (-135.5683 ± 45.8415 kcal/mol and -166.8876 ± 17.7874 kcal/mol, respectively) compared to BbTX-III (-120.0387 ± 7.4546 kcal/mol and -114.3389 ± 15.4885 kcal/mol, respectively). Furthermore, these acids reduced myotoxicity, hemorrhage, hemostatic disturbances, and kidney and liver injuries, as well as leukogram and platelet alterations induced by B. brazili venom. The chlorogenic and rosmarinic acids demonstrated antiophidic potential by inhibiting both the local and systemic effects of envenomation. These findings suggest that their potential use as complementary therapies against envenomation caused by B. brazili.