Adriamycin and altered membrane functions in rat hearts.
To evaluate the potential roles of alterations of membrane functions and resulting calcium overload in the pathogenesis of acute adriamycin cardiotoxicity, we observed sarcolemmal, sarcoplasmic reticular and mitochondrial functions in isolated hearts perfused by the Langendorff technique and exposed to adriamycin. Myocardial tissue calcium content was increased to 120 and 130% of the control level after 30 and 60 min perfusion with adriamycin (50 micrograms/ml), respectively. Sarcolemmal ouabain-sensitive Na+,K+-ATPase activity was decreased by 46% after 30 min perfusion, compared with the control. Mitochondrial calcium uptake was also depressed but sarcoplasmic reticular calcium uptake and binding remained unaltered. Mitochondrial respiratory activity was depressed after 60 min perfusion, when glutamate was used as a substrate, thereby indicating that adriamycin had an inhibitory effect on the NADH-dehydrogenase system. Thus, among membrane functions directly or indirectly regulating calcium movement, the inhibition of enzyme systems susceptible to lipid peroxidation may play important roles in calcium overload induced by adriamycin.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D004317:Doxorubicin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium