Preliminary neurological evaluation of generalized weakness in zinc pyrithione-treated rats

Abstract

Male rats were fed ad lib. a diet containing 250 ppm zinc pyrithione for 10 days and were then given the basic, untreated, diet for the rest of the study. Initial clinical signs of locomotor abnormalities were observed after the rats had been on the treated diet for 8–10 days. Progressive hind-limb weakness with accompanying muscle atrophy was a constant finding. Muscles of the forelegs and the chest appeared normal and showed almost normal function. The back muscles seemed involved, since kyphosis developed without skeletal abnormality. Weight loss was significantly greater and recovery significantly slower in treated rats than in matched pair-fed controls. Neurophysiological studies of sciatic-nerve conduction velocities failed to show differences between treated and control animals. A significant difference in contraction was noted between normal and affected muscles in that treated animals with marked muscle atrophy had a weaker contractile response to a greater electrical sciaticnerve stimulus than had the controls. This study suggests that the lesion is at the subcellular level and the muscle atrophy may be caused by a basic abnormality in neural conduction, by dysfunction at the myoneural junction or in the muscle-fibre membrane or by a change at the molecular level in the muscle fibres.