The effects of chronic isoniazid intoxication on motor end plate sprouting in rat sternocostalis muscle and on responses to partial denervation and local botulinum toxin.

Abstract

Chronic dosing of rats with isoniazid (INH) leads to an increase in the incidence of short "spontaneous" sprouts on motor end plates in the rat sternocostalis muscle. After partial denervation there is a slight increase in terminal sprouting after 1 week of dosing: this changes to a significant decrease from 2 to 6 weeks of dosing. The same is noted after local botulinum toxin injection, and in both conditions sprout length is significantly reduced. In vitro studies show that glutathione, cysteine and cystathionine all increase the incidence of short, "spontaneous" sprouts from end plates, while homocysteine and cystine have no effect. These findings are interpreted in the light of the hypothesis that in INH intoxication there may be a reduction of available axonal glutathione and cysteine due to inhibition of the pyridoxal phosphate-dependent enzymes cystathionine synthetase and cystathioninase .