Effects of various drugs on denervation changes in rat muscles

The effects of drugs, known to affect lysosomal enzyme activities on denervated gastrocnemius muscles of rats were studied. The drugs used were: amiodarone, chloroquine, cortisone, streptomycin and trypan blue. The parameters investigated included changes in fibrillations in electromyographs, morphometric evaluations of muscle atrophy and replacement, and light and electron microscopic analysis of morphological changes and of histochemical acid phosphatase activity. All drug treatments reduced the intensity and frequency of fibrillations. Acid phosphatase spillage was best inhibited by trypan blue. Progressive muscle fiber atrophy with massive aggregation of mitochondria at the cell periphery occurred in denervated fibers. Atrophy was expressed both in loss of muscle weight and in reduction of average muscle fiber diameter. Administration of all the drugs resulted in slowing down of muscle weight loss, particularly 30 days after denervation. All drugs induced slowing down of the loss in average fiber diameter on day 3 after denervation, while on day 10 only cortisone and amiodarone still exerted this effect. A similar transitory slowing of denervation changes was observed in estimations of replacement of muscle by collagen and adipose tissue. Only the effect of trypan blue and amiodarone persisted on day 10. The results indicate that drugs known to inhibit lysosomal enzyme activity may slow down the denervation-derived muscle atrophy to a certain extent, but the effects are transitory.