Electron spin resonance studies on the mechanism of adriamycin-induced heart mitochondrial damages.
Rats were given i.p. injections of Adriamycin (4 mg/kg body weight) for 6 consecutive days. Electron spin resonance spectrometry with spin labeling and a trapping technique was applied to heart mitochondria obtained from treated and control animals, in order to examine the physical response of heart mitochondrial membrane affected by Adriamycin. The Adriamycin treatment resulted in a decrease of membrane fluidity (and an increase in order parameter S), with concomitant dysfunction of respiratory responses. The generation of hydroxyl radicals from mitochondria was enhanced in the Adriamycin-treated group. In addition, superoxide dismutase activity in the mitochondrial matrix was found to decrease. The heart mitochondria of Adriamycin-treated animals contained a large amount of lipid peroxide. These results suggest that the enhancement of hydroxyl radical formation in mitochondria affected by Adriamycin is one of the factors involved in Adriamycin-induced cardiotoxicity.
Ogura
R
R
Department of Medical Biochemistry, Kurume University School of Medicine, Japan.
Sugiyama
M
M
Haramaki
N
N
Hidaka
T
T
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism
D005609:Free Radicals; D004317:Doxorubicin; D013482:Superoxide Dismutase