ULTRASTRUCTURAL FEATURES OF ADRIAMYCIN-INDUCED SKELETAL AND CARDIAC-MUSCLE TOXICITY

  • 1 January 1985
    • journal article
    • research article
    • Vol. 118  (2) , 288-297
Abstract
The effect of the antitumor agent adriamycin, a known cardiotoxin, on mouse heart, diaphragm and gastrocnemius muscle was examined. Using an established model of adriamycin cardiac toxicity, 4 days after the i.p. injection of 20 mg/kg of adriamycin, characteristic heart lesions, including vacuolation of the sarcoplasmic reticulum, interstitial edema and mitochondrial degeneration, were demonstrated in all treated animals. Similar, but much more severe, myocyte damage was demonstrated in the diaphragm; muscle toxicity followed a decreasing gradient of injury from the peritoneal to the thoracic surface of the tissue. Treatment with adriamycin resulted in an increase in the size and number of lipid droplets in the red fibers of the gastrocnemius muscle without any other ultrastructural evidence of drug-induced damage to myocytes. An examination of the pharmacokinetics and metabolism of adriamycin after i.p. treatment revealed that relative drug levels in muscle (diaphragm .mchgt. heart .mchgt. gastrocnemius) paralleled the degree of ultrastructural damage observed. Evidently, treatment with adriamycin can produce significant injury to noncardiac muscle in a fashion that strongly resembles the characteristic pattern of adriamycin-related damage to the heart and the degree of myocyte damage is apparently dependent upon the adriamycin concentration in the tissue.