title: Poor regenerative outcome after skeletal muscle necrosis induced by Bothrops asper venom: alterations in microvasculature and nerves.
abstract: BACKGROUND
  Viperid snakebite envenoming is characterized by prominent local tissue damage, including muscle necrosis. A frequent outcome of such local pathology is deficient skeletal muscle regeneration, which causes muscle dysfunction, muscle loss and fibrosis, thus provoking permanent sequelae that greatly affect the quality of life of patients. The causes of such poor regenerative outcome of skeletal muscle after viperid snakebites are not fully understood.
  
  
  RESULTS
  A murine model of muscle necrosis and regeneration was adapted to study the effects of the venom and isolated toxins of Bothrops asper, the medically most important snake in Central America. Gastrocnemius muscle was injected with either B. asper venom, a myotoxic phospholipase A(2) (Mtx), a hemorrhagic metalloproteinase (SVMP), or saline solution. At various time intervals, during one month, tissue samples were collected and analyzed by histology, and by immunocytochemical and immunohistochemical techniques aimed at detecting muscle fibers, collagen, endothelial cells, myoblasts, myotubes, macrophages, TUNEL-positive nuclei, and axons. A successful regenerative response was observed in muscle injected with Mtx, which induces myonecrosis but does not affect the microvasculature. In contrast, poor regeneration, with fibrosis and atrophic fibers, occurred when muscle was injected with venom or SVMP, both of which provoke necrosis, microvascular damage leading to hemorrhage, and poor axonal regeneration.
  
  
  CONCLUSIONS
  The deficient skeletal muscle regeneration after injection of B. asper venom is likely to depend on the widespread damage to the microvasculature, which affects the removal of necrotic debris by phagocytes, and the provision of nutrients and oxygen required for regeneration. In addition, deficient axonal regeneration is likely to contribute to the poor regenerative outcome in this model.
authors.affiliation: Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala. [corrected].
authors.forename: Rosario
authors.initials: R
authors.lastname: Hernández
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabalceta
authors.forename: Patricia
authors.initials: P
authors.lastname: Saravia-Otten
authors.forename: Alessandra
authors.initials: A
authors.lastname: Chaves
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rucavado
mesh_terms: D000818:Animals; D003435:Crotalid Venoms / Q000633:toxicity*; D003893:Desmin / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000633:toxicity; D006470:Hemorrhage / Q000139:chemically induced; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008666:Metalloendopeptidases / Q000633:toxicity; D051379:Mice; D055806:Microvessels / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation; D009336:Necrosis / Q000139:chemically induced; D051763:PAX7 Transcription Factor / Q000378:metabolism
chemical_list: D003435:Crotalid Venoms; D003893:Desmin; D051763:PAX7 Transcription Factor; D054501:Group II Phospholipases A2; C104933:BaP1 metalloproteinase; D008666:Metalloendopeptidases