The role of lipid peroxidation in acute doxorubicin-induced cardiotoxicity as studied in rat isolated heart.
Doxorubicin induces an acute cardiotoxicity that becomes manifest in isolated hearts as a deterioration in mechanical function. The oxidative component in this myocardial damage has been investigated. The effects of doxorubicin on the activity of superoxide dismutase and the capacity of the glutathione system, factors of the cellular protective mechanism against free radicals, were examined in rat isolated heart. Doxorubicin was found to reduce the capacity of the protective mechanisms. Whether oxidative membrane damage due to excessive free radical formation plays a role in the pathogenesis of the acute cardiotoxic action of doxorubicin was also examined. Its acute effect on myocardial contraction amplitude, frequency of beating, coronary flow and on the above mentioned biochemical parameters was compared in rat hearts sufficient or deficient in vitamin E. Peroxidation of lipids was measured as the formation of malondialdehyde, one of the final products of this process. Vitamin E deficiency neither aggravated the decrease in the capacity of the cellular protective factors nor worsened the reduction in myocardial function. Nor did induction of lipid peroxidation by doxorubicin occur in vitamin E-deficient hearts. It was concluded that lipid peroxidative damage most probably is not decisive in the development of the acute cardiomyopathy in rats.
Julicher
R H
RH
Sterrenberg
L
L
Bast
A
A
Riksen
R O
RO
Koomen
J M
JM
Noordhoek
J
J
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000503:physiopathology
D008054:Lipid Peroxides; D008315:Malondialdehyde; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione