Characterization of the oxidation products of BO-653 formed during peroxyl radical-mediated oxidation of human plasma.
4,6-Di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranol (BO-653) is a novel antioxidant synthesized by theoretical findings and considerations. Here we report on the aqueous peroxyl radical-induced oxidation of human plasma in the presence of BO-653. When BO-653 was given to healthy human subjects at 400 mg twice daily for 28 days, lipids in the resulting plasma were protected from oxidation compared with lipids present in plasma from subjects receiving placebo. Similarly, BO-653 added in vitro at 50 muM inhibited the peroxyl radical-induced accumulation of cholesteryl ester hydroperoxides that occurred in the presence of alpha-tocopherol, although BO-653 did not decrease the rate of consumption of ascorbate, albumin-bound bilirubin, and uric acid. The antioxidant action of in vivo and in vitro added BO-653 was associated with the formation of two major reaction products of BO-653, the structures of which were elucidated by mass spectrometry and nuclear magnetic resonance analyses. The products were identified as stereoisomers of dioxybis(4,6-di-tert.-butyl-2,3,5,7a-tetrahydro-2,2-dipentylbenzofuran-5-one). These dialkylperoxides of BO-653 might be useful markers to assess the antioxidant function of BO-653 in biological systems in vivo.
Yamauchi
Ryo
R
Centre for Vascular Research, University of New South Wales, and Department of Haematology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Southwell-Keely
Peter
P
Suarna
Cacang
C
Ray
Sangeeta
S
Raftery
Mark
M
Cynshi
Osamu
O
Stocker
Roland
R
D000418:Albumins / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D001663:Bilirubin / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism; D013237:Stereoisomerism; D014527:Uric Acid / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000418:Albumins; D000975:Antioxidants; D001572:Benzofurans; D002788:Cholesterol Esters; D010545:Peroxides; C081459:cholesteryl ester hydroperoxide; D014527:Uric Acid; C049375:perhydroxyl radical; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D001663:Bilirubin