Effect of selenium-vitamin E on adriamycin-induced cardiomyopathy in rabbits.
Administration of selenium-vitamin E (Se-E) to weanling rabbits chronically treated with adriamycin (ADR) resulted in decreased incidence and severity of cardiomyopathy and decreased cumulative mortality during a 10-week experiment. However, Se-E did not protect against extracardiac lesions or against a number of clinicopathologic alterations induced by chronic ADR toxicosis. Histopathologic alterations of ADR-induced cardiomyopathy were concentrated periarterially in the free and septal walls of the left ventricle. Initial vacuolar degeneration of injured cardiac muscle cells was followed by myofibrillar lysis and eventual cell death with subsequent interstitial fibrosis. Ultrastructurally, degenerated cardiac muscle cells had 3 prominent alterations: (1) sarcoplasmic vacuolization caused by distention of elements of sarcoplasmic reticulum and T-tubules, (2) degeneration of mitochondria forming large myelin figures from disrupted membranes, and (3) lysis of myofibrils producing granular sarcoplasmic masses. Severely injured fibers were necrotic and macrophages invaded to remove cellular debris. The interstitium was distended by edema and increased amounts of collagen. Extracardiac lesions in rabbits with chronic ADR toxicosis included the usually recognized alterations involving cell-renewal systems in kidney, testis, bone marrow, skin, and alimentary tract, as well as vacuolar degeneration of skeletal muscle and focal loss of pancreatic tissue, with ensuing pancreatic fibrosis and fat necrosis. Deaths in ADR-treated rabbits usually were precipitated by terminal septic embolism. The partial protection afforded by Se-E against ADR-induced cardiomyopathy may be associated with stabilization of the membranes of injured muscle cells or with prevention of ADR-induced inhibition of coenzyme Q10-dependent mitochondrial enzymes.
D000505:Alopecia / Q000662:veterinary; D000818:Animals; D003872:Dermatitis / Q000662:veterinary; D004317:Doxorubicin; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D007668:Kidney / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000648:ultrastructure; D010179:Pancreas / Q000473:pathology; D011817:Rabbits; D012643:Selenium / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology; D014810:Vitamin E / Q000627:therapeutic use*
D014810:Vitamin E; D004317:Doxorubicin; D012643:Selenium