Local Tissue Damage Induced by Snakebite Envenoming: Mechanisms and Therapeutic Advances.

Snakebite envenoming is a serious and often neglected tropical disease associated with high mortality and disability rates. Local tissue injury is one of the main causes of long-term functional impairment after snakebite. Clinically, it may present as local hemorrhage, edema, myonecrosis, and tissue fibrosis. Accumulating evidence indicates that several venom components, including snake venom metalloproteinases, snake venom phospholipase A2s, three-finger toxins, and L-amino acid oxidases, are involved in local tissue injury. These toxins can induce direct cellular and microvascular damage. They can also trigger inflammatory responses, immune dysregulation, and oxidative stress. Compared with systemic toxicity, local tissue damage often has more persistent effects on patients. Antivenom is currently the main treatment of snakebite envenoming. It can neutralize venom toxins and reduce mortality. However, its effect on established local tissue injury remains limited. In recent years, several adjunctive therapies have shown potential. These include small-molecule enzyme inhibitors, photobiomodulation therapy, and stem cell-based therapies. However, most studies still lack sufficient clinical evidence. This review summarizes the major venom components involved in snakebite-induced local tissue injury, the underlying pathophysiological mechanisms, and potential therapeutic strategies. The aim of this review is to provide new perspectives for future mechanistic studies and clinical intervention.