Morphological changes induced by a generalized myotoxin (myoglobinuria-inducing toxin) from the venom of Pseudechis australis (king brown snake) in skeletal muscle and kidney of mice.

A myotoxin causing myoglobinuria was isolated from the venom of Pseudechis australis (PA myotoxin). Myoglobinuria was observed in mice 60 min post-injection (4.5 mg/kg i.m.) into calf muscles. Light microscopic observation revealed hypercontraction of muscle fibres with delta lesions and vacuolation. Severe necrosis was observed as early as 30 min. Infiltration of the muscle fibres with macrophages was seen by 3 hr with peak infiltration by 12-48 hr. Electron microscopic study showed pathological changes in skeletal muscle as early as 5 min. Electron microscopic study showed disruption of the sarcolemma with dissolution and degeneration of the Z-band. Degeneration of the I-band was followed by degenerative changes in the A-band. Regeneration of muscle was evident by 3-5 days by the presence of many myotubes containing central nuclei. Regeneration was almost complete by 3 weeks. Contralateral soleus muscle which was not injected with toxin also showed degeneration followed by regeneration with central nuclei. Light microscopic studies of kidney showed myoglobin casts in both proximal and distal tubules, collecting ducts and loops of Henle. We conclude that this myotoxin probably acts on the Z-disc structures and also causes renal damage due to 'myoglobin cast nephropathy'.