Inhibition of lipid peroxidation by spin labels. Relationships between structure and function
Inhibition of lipid peroxidation by nitroxide radicals and their corresponding hydroxylamines was investigated. The nitroxides were either oxazolidines or piperidines, differing in substitution of the backbone of the molecule (a five or six-membered ring structure, respectively). Concentration requirements for 50% inhibition of microsomal lipid peroxidation varied from 340 to 6 microM for the nitroxides, and from 120 to 3 microM for the hydroxylamines, correlating with lipophilicity and chemical structure. Intramembrane concentrations required for 50% inhibition was independent of lipophilicity when peroxidation was initiated with ADP-Fe2+ but increased with lipophilicity when peroxidation was initiated with t-butylhydroperoxide. During studies of the kinetics of the inhibition, two modes were seen: a delay or a decreased rate of the process. The former mode was seen with the more lipophilic inhibitors. The mechanism of inhibition was similar for all nitroxides and consisted of the following three major components: blocking of primary initiation, prevention of secondary (peroxide-dependent) initiation, and scavenging of various lipoid radicals in the membrane, the major mode of action of the hydroxylamines. Inhibitory efficiency was interpreted in terms of steric hindrance, diffusibility, regeneration of inhibitor, and ability to interact with hydrophilic sites in a hydrophobic environment.
- Research Organization:
- Chalmers Univ. of Technology, Goeteborg (Sweden)
- OSTI ID:
- 5814183
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 264:19
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROXYLAMINE
BIOLOGICAL EFFECTS
LIPIDS
METABOLISM
NITROXYL RADICALS
ADP
INHIBITION
LIVER
MICROSOMES
MOLECULAR STRUCTURE
NITROGEN OXIDES
OXAZOLES
PIPERIDINES
RATS
STRUCTURE-ACTIVITY RELATIONSHIPS
AMINES
ANIMALS
AZINES
AZOLES
BODY
CELL CONSTITUENTS
CHALCOGENIDES
DIGESTIVE SYSTEM
GLANDS
HETEROCYCLIC COMPOUNDS
MAMMALS
NITROGEN COMPOUNDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PYRIDINES
RADICALS
RIBOSOMES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology