Generation of free radicals from model lipid hydroperoxides and H[sub 2]O[sub 2] by Co(II) in the presence of cysteinyl and histidyl chelators
- National Cancer Institute, Frederick, MD (United States)
- West Virginia Univ., Morgantown, WV (United States)
Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H[sub 2]O[sub 2] at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxy (OH) radicals. Oxidized glutathione and cysteine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH or t-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, homocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H[sub 2]O[sub 2] produced only a small amount of OH radicals. Addition of glutathione to the mixture of Co(II) and H[sub 2]O[sub 2] resulted in generation of both glutathionyl (GS) and OH radicals, which could be inhibited by DTPA and deferoxamine. Deferoxamine nitroxide radical was produced from deferoxamine incubated with Co(II) and H[sub 2]O[sub 2]. 36 refs., 7 figs., 3 tabs.
- OSTI ID:
- 6788564
- Journal Information:
- Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 6:3; ISSN 0893-228X; ISSN CRTOEC
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
AROMATICS
AZOLES
BIOSYNTHESIS
CARBOXYLIC ACIDS
CARCINOGENESIS
CHELATING AGENTS
COBALT
CUMENE
CYSTEINE
DEFEROXAMINE
DRUGS
DTPA
ELECTRON SPIN RESONANCE
ELEMENTS
GLUTATHIONE
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HISTIDINE
HYDROCARBONS
IMIDAZOLES
MAGNETIC RESONANCE
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PATHOGENESIS
PENICILLAMINE
PEPTIDES
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
RESONANCE
RESPONSE MODIFYING FACTORS
SYNTHESIS
THIOLS
TRANSITION ELEMENTS