Skeletal muscle regeneration after myonecrosis induced by Bothrops asper (terciopelo) venom

In order to assess the extent of regeneration, creatine kinase content of injected gastrocnemius muscle were determined at four time intervals after inoculation. Simultaneously, the diameters of regenerating fibers were measured, the wet weight of the gastrocnemius was recorded and electrophoretic patterns of muscle proteins and histology of the tissue were analyzed. Injection of crude B. asper venom caused myonecrosis and hemorrhage; in these cases regeneration was very poor, as there was only a small increase in creatine kinase content by four weeks. Histologically, large areas of fibrosis were observed, intermixed with small areas of regenerating muscle. Furthermore, the diameter of regenerating muscle cells was abnormally small, even four weeks after envenomation. In order to test the role of hemorrhage in impairment of regeneration, we also studied the effects of B. asper venom that had been incubated with a volume of antivenom that completely neutralized hemorrhagic activity, but not myotoxic activity. At 24 hr mice showed a generalized picture of myonecrosis, without hemorrhage. Afterwards, regeneration proceeded and significant increases in creatine kinase content were demonstrated at 1, 2 and 4 weeks. Also, histological observations showed the presence of many areas of regenerating muscle, intermixed with small areas of fibrosis and adipose tissue. The diameter of regenerating cells increased with time, reaching values of 25.8 microns by four weeks. Electrophoretic analyses of muscle proteins showed that muscle injected with partially neutralized venom underwent a more complete regeneration than muscle injected with crude venom.(ABSTRACT TRUNCATED AT 250 WORDS)