Morphological Changes in Skeletal Muscle Following Experimental Colchicine Toxicity: Electron Microscopic Study

ABSTRACT

To investigate the morphological changes in skeletal muscle produced by colchicines toxicity, 42/rats were given a single intraperitoneal dose(0.4mg/Kg) of colchicines, and the animals were killed at daily intervals up to 7 days. The results of light microscopic and electron microscopic observations are summarized as follows; 1) At the light microscopic level, colchicines treated arts show non-inflammatory, nonspecific scattered degeneration or necrosis of myofibers irrespective of location of the skeletal muscle. No significant pathologic changes in peripheral nerve fibers distributed in affected muscles are seen. 2) The general ultrastructural changes are dilation of sarcoplasmic reticulum, swelling and pleomorphism of mitochondria, and appearance of membraneous bodies characterized by a single or multiple concentric layers of membranes in subsarcolemmal zones and intermyofibrillar zones, and focal necrosis or loss of myofibrils. The incidence and severity of these changes show gradual increase and reach maximal peak 3 days after colchicines administration, and then they show gradual decrease. Nerve fibers and motor-end plates show no difference compared with the control. 3) The observations are consistent with the opinion that the muscle weakness or paresis produced by toxic dose of colchicines is not of neuropathic, but of myopathic alterations. 4) The membraneous bodies are classified into the following 3 types;Type I is those bodies outlined by a few concentric membranes with osmiophilic granules, small vesicles, free ribosomes, and mitochondria in central zone. Type II is those outlined by several concentric layers of membranes with osmiophilic granules, small vesicles, free ribosomes, and mitochondria in center. Type III is those outlined by multilayered or thick concentric membranes with osmiophilic granules, small vesicles, free ribosomes, and mitochondria in central zone, frequently with complicated lamellar structures. 5) The skeletal muscle lesions produced by colchicines toxicity may be categorized into those degenerative changes characterized by the appearance of membraneous bodies. And, morphologically, it is presumed that the membraneous bodies are heterogenous in origin, alterations of subcellular structures such as sarcoplasmic reticulum, mitochondria, and lysosome.