A new class of free radical scavengers reducing adriamycin mitochondrial toxicity.
Beef heart mitochondria were incubated with ADM and NADH. An adriamycin semiquinone radical was detected using ESR spectroscopy. The semiquinone radical production rate is decreased upon addition of a scavenger (AD 20) in the reaction medium. NMRI mice were treated with AD 20 (70 mg/kg, i.p.) 15 min prior ADM injection (20 mg/kg, i.p.) or with ADM alone. Heart mitochondria were isolated 48 hr later. The enzymatic activities of complex I-III and complex IV of the mitochondrial respiratory chain were strongly depressed in animals receiving ADM alone, whereas these activities were almost completely restored in animals receiving AD 20 and ADM. Fluorescence depolarization measurements indicated that only mice treated with ADM alone presented a decreased fluidity of their cardiac mitochondrial membrane.
Praet
M
M
Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles, Belgium.
Calderon
P B
PB
Pollakis
G
G
Roberfroid
M
M
Ruysschaert
J M
JM
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D008929:Mitochondria, Heart / Q000187:drug effects; D009245:NADH Dehydrogenase / Q000378:metabolism
D005609:Free Radicals; D008054:Lipid Peroxides; C053274:AD 20; D004317:Doxorubicin; D009245:NADH Dehydrogenase; D000409:Alanine