Effects of Phospholipase A2 and Metalloproteinase Inhibitors on Skeletal Muscle Regeneration After Myonecrosis Induced by the Venom of Bothrops asper: An Initial Assessment in Mice

Skeletal muscle regeneration is often impaired after acute muscle damage induced by viperid snake venoms, such as that of Bothrops asper, a medically relevant species in Latin America. It has been shown that traces of venom that remain in the damaged muscle affect myogenic cells in culture, raising the possibility of inhibiting these toxins during the regenerative process to improve regeneration. Using a mouse model of myonecrosis and regeneration, we evaluated the effects of Varespladib (a phospholipase A2 inhibitor) or Marimastat (a metalloproteinase inhibitor) on muscle regeneration when administered intravenously 24 h after the onset of myonecrosis, i.e., after muscle damage has occurred. The regenerative process was evaluated 14 and 28 days after venom injection. Marimastat, or a combination of both inhibitors, increased the number and diameter of regenerating muscle fibers and reduced tissue fibrosis compared to tissues from mice receiving only venom, as judged by qualitative and quantitative histological assessment. These initial results underscore the deleterious role of traces of venom components, especially metalloproteinases, in damaged muscles during muscle regeneration.