Compromised Regeneration, Damage to Blood Vessels and the Endomysium Underpin Permanent Muscle Damage Induced by Puff Adder (Bitis arietans) Venom.

The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common consequence of B. arietans envenomation that can result in long-term morbidity and even death. Antivenom treatment can mitigate the systemic effects of the venom but offers little protection against local tissue damage. Identifying the mechanisms through which B. arietans venom induces tissue damage and impedes skeletal muscle regeneration could identify possible treatment alternatives that could help alleviate the long-term consequences of envenomation. Skeletal muscle has an innate ability to regenerate, but constituents within the venom can impede multiple stages of this regeneration process. In this study, we employed a combination of biochemical analyses, cell-based assays, and in vivo experiments to assess the toxicological implications of B. arietans envenomation and its impacts on key processes of regeneration. Our findings demonstrate that the pathological characteristics of permanent muscle damage resulting from B. arietans envenomation may be attributed to the venom's effects on muscle stem cell precursors, the extracellular matrix (ECM), and the influence of blood-borne proteins that promote fibrosis.