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American Journal of Pathology, Vol 118, 288-297, Copyright © 1985 by American Society for Investigative Pathology

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Ultrastructural features of Adriamycin-induced skeletal and cardiac muscle toxicity

JH Doroshow, C Tallent and JE Schechter

In this study, the authors examined the effect of the anti-tumor agent Adriamycin, a known cardiotoxin, on mouse heart, diaphragm, and gastrocnemius muscle. Using an established model of Adriamycin cardiac toxicity, they found that 4 days after the intraperitoneal 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. Furthermore, 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. On the other hand, 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 intraperitoneal treatment revealed that relative drug levels in muscle (diaphragm much greater than heart much greater than gastrocnemius) paralleled the degree of ultrastructural damage observed. This study indicates that treatment with Adriamycin can produce significant injury to non-cardiac muscle in a fashion that strongly resembles the characteristic pattern of Adriamycin-related damage to the heart, and that the degree of myocyte damage is apparently dependent upon the Adriamycin concentration in the tissue.

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