Effects of Adriamycin on heart mitochondrial function in rested and exercised rats.
The effect of Adriamycin (ADM) administration on heart mitochondria was investigated in rats at rest and after an acute bout of maximal exercise. ADM was given intravenously at a dosage of 8 mg/kg body weight 24 and 1 hr before rats were decapitated. Respiratory functions of the isolated heart mitochondria were measured polarographically with both site 1 (pyruvate-malate and 2-oxoglutarate) and site 2 (succinate) substrates. State 4 (basal) respiration was increased using all substrates in ADM-treated rat hearts compared with non-drug control hearts. The mitochondrial respiratory control index was decreased with ADM, but the reduction was due to an increase in state 4 rather than a decrease of state 3 (ADP-stimulated) respiration. ADM administration abolished an exercise-induced elevation of state 3 respiration using all substrates. There was no significant myocardial oxidative damage of dysfunction as evaluated by lipid peroxidation and antioxidant enzyme activity. Addition of exogenous free radicals to the respiratory medium using hypoxanthine and xanthine oxidase resulted in significant deterioration of mitochondrial function in all parameters measured, but no drug- or exercise-specific patterns of damage were revealed. It is concluded that the current dose of ADM (20% of the established cumulative toxic dose) administered within 24 hr can interfere with normal heart mitochondrial function both at rest and during heavy exercise, but does not elicit overwhelming oxidative damage to the myocardium.
Ji
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LL
Division of Nutritional Sciences, University of Illinois, Urbana 61801.
Mitchell
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EW
D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest / Q000502:physiology
D005609:Free Radicals; D004317:Doxorubicin