Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage
- School of Medicine, Hebrew Univ., Jerusalem (Israel)
The protective effect of stable nitroxide radicals against oxidative damage was studied using cardiomyocyte cultures obtained from newborn rats. Monolayered cardiomyocytes were exposed to H{sub 2}O{sub 2} and the effect on spontaneous beating and leakage of LDH was determined. Hydrogen peroxide irreversibly blocked rhythmic beating and resulted in a significant membrane injury as shown by release of LDH. The injury was prevented by catalase which removes H{sub 2}O{sub 2} and by cell-permeable, metal-chelating agents such as desferrioxamine or bipyridine. In contrast, reagents which are excluded from the cell such as superoxide dismutase or DTPA did not protect the cells against H{sub 2}O{sub 2}. Five- and six-membered ring, stable nitroxide radicals which have previously been shown to chemically act as low-molecular weight, membrane-permeable, SOD-mimetic compounds provided full protection. The nitroxides prevented leakage of LDH and preserved normal cardiomyocyte contractility, presumably by intercepting intracellular O{sub 2}-radicals. Alternatively, protection may result through nitroxides reacting with reduced transition metal ions or by detoxifying secondary organic radicals.
- OSTI ID:
- 5545992
- Journal Information:
- Journal of Clinical Investigation; (USA), Vol. 87:5; ISSN 0021-9738
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROGEN PEROXIDE
TOXICITY
NITROGEN OXIDES
BIOLOGICAL EFFECTS
ANIMAL CELLS
CHELATING AGENTS
DEFEROXAMINE
HEART
HYDROXIDES
LACTATE DEHYDROGENASE
MYOCARDIUM
RADICALS
RATS
REDOX REACTIONS
AMINES
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
CHALCOGENIDES
CHEMICAL REACTIONS
ENZYMES
HEMIACETAL DEHYDROGENASES
HYDROGEN COMPOUNDS
MAMMALS
MUSCLES
NITROGEN COMPOUNDS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology