Establishment of an animal model for myoglobinuria by use of a myotoxin from Pseudechis australis (king brown snake) venom in mice.

A new laboratory animal model for studying the pathologic mechanisms of myoglobinuria in mice after envenomation with Pseudechis australis snake venom or its myotoxin has been established. The experimental mice (Swiss albino) had myoglobinuria 60 min after administration of the venom, as indicated by red or dark-brown urine. Light microscopic studies revealed myonecrosis of the locally injected soleus muscle 30 min after exposure to the myotoxin, followed by regeneration in 7 to 10 days. Electron microscopic studies of the soleus muscle revealed fragmentation and dissolution of the Z disk, followed by degeneration of the sarcomere. Light microscopy of the kidneys revealed numerous pigmented casts filling the lumen of the tubules; some tubules had features of acute tubular necrosis. Immunohistochemical localization of myoglobin by the immunoperoxidase method confirmed myoglobin casts in the renal tubules. Electron microscopy of the kidneys also revealed intratubular casts composed of markedly electron-dense material filling the lumen. These results indicate that rhabdomyolysis caused by the venom or toxin is followed by myoglobinuria, with renal manifestations in the form of myoglobin cast nephropathy and tubulopathy. This mouse model of experimental snake venom-induced myoglobinuria is an ideal model for investigating the entire sequence of myoglobinuria and related cast nephropathy.