Effects of dithiobiuret intoxication on motor end plates in sternocostalis and hindlimb muscles of female rats.

Daily dosing with 1-3 mg/kg dithiobiuret for 4-5 days causes progressive, generalised muscle weakness which is fatal in about 50% of cases on day 4 or 5. Survivors recover mobility by day 7 and appear normal, although still weak. Striking changes in the motor nerves and motor end plates can be observed before and during the development of this weakness, using the zinc iodide-osmium staining technique. The terminal internodes of intramuscular axons become densely stained: later this may extend back into the main intramuscular (i.m.) nerves, and is often followed by axonal degeneration. Many motor end plates lose their branching form and become globular, and profuse terminal sprouting develops before any nerve degeneration appears. Following axonal degeneration, collateral sprouting becomes prominent, and, within four weeks of beginning the dose regime, restores the normal appearance of the innervation. This pattern of response was observed clearly in the whole mounts of the sternocostalis muscle: similar but less marked changes occurred in the lumbrical muscles, while in the soleus and tibialis anterior muscles, loss of end plates seemed to be a more common response. Despite marked differences in the severity of the functional disability, the i.m. changes were similar in juvenile and adult rats. These changes are related to previous electrophysiological findings on the possible mechanism of action of dithiobiuret.