Histopathological alterations, local hemorrhage and myotoxic effects induced by Bothrops mattogrossensis venom and an acidic isolated phospholipase A₂.

Snakebite envenomation is a neglected tropical disease with major health impacts in Latin America, where Bothrops species are responsible for vast majority of accidents. Among them, Bothrops mattogrossensis is epidemiologically relevant due to its wide distribution and clinical involvement in envenomation. This study aimed to characterize the histopathological and biochemical effects of B. mattogrossensis venom (BmV) and its isolated acidic phospholipase A₂ (BmPLA₂-A) in mice. Skeletal muscle, heart, lung, liver, kidney, and spleen were analyzed histologically, while local toxic effects were assessed through hemorrhagic activity and creatine kinase (CK) release. BmPLA₂-A induced discrete and non-significant vascular injury, inflammation, and fibrosis in skeletal muscle, along with vascular congestion and hemorrhagic foci in the heart, lungs, and kidneys. However, it did not produce measurable hemorrhagic halos or significant CK elevation, indicating limited hemorrhagic and myotoxic potential. In contrast, crude venom caused more intense and heterogeneous alterations, including extensive vascular ectasia, hemorrhage, pulmonary fibrosis, and pronounced CK elevation, demonstrating strong myotoxic and hemorrhagic activity. BmPLA₂-A and BmV induced significant hepatic vascular congestion and increased Kupffer-cell activity, with preserved hepatocyte morphology and discrete sinusoidal disorganization. Splenic tissue remained preserved, showing significant vascular congestion only in the venom-treated group. These findings demonstrate that BmPLA₂-A contributes to local inflammation and vascular damage but is not the main determinant of systemic hemorrhage or muscle necrosis, which are primarily mediated by other venom components. From a translational perspective, the identification of catalytically active yet non-myotoxic PLA₂s such as BmPLA₂-A opens avenues for pharmacological exploration, providing potential molecular tools for probing lipid signaling and therapeutic innovation.