Generation of free radicals from model lipid hydroperoxides and H2O2 by Co(II) in the presence of cysteinyl and histidyl chelators.
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 H2O2 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 hydroxyl (.OH) radicals. Oxidized glutathione and cystine 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 ort-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 H2)2 produced only a small amount of .OH radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Shi
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Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Dalal
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NS
Kasprzak
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D000111:Acetylcysteine / Q000737:chemistry; D000861:Anserine / Q000494:pharmacology; D000440:Butanols / Q000737:chemistry; D002336:Carnosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D003035:Cobalt / Q000737:chemistry* / Q000633:toxicity; D003545:Cysteine / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry; D005998:Glycine / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008054:Lipid Peroxides / Q000737:chemistry* / Q000378:metabolism; D010396:Penicillamine / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D020002:tert-Butyl Alcohol
D000440:Butanols; D002614:Chelating Agents; D005609:Free Radicals; D008054:Lipid Peroxides; D010446:Peptide Fragments; C005038:homocarnosine; D003035:Cobalt; D006639:Histidine; D002336:Carnosine; D006861:Hydrogen Peroxide; D005978:Glutathione; D010396:Penicillamine; D000861:Anserine; D003545:Cysteine; D020002:tert-Butyl Alcohol; D005998:Glycine; D000111:Acetylcysteine