Biomaterial Database

Free radical intermediates during peroxidase oxidation of 2-t-butyl-4-methoxyphenol, 2,6-di-t-butyl-4-methylphenol, and related phenol compounds. 1989

M Valoti, and H J Sipe, and G Sgaragli, and R P Mason

Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

2-t-butyl-4-methoxyphenol (BHA) and 2,6-di-t-butyl-4-methylphenol (BHT) are widely used antioxidant food additives that are generally recognized as safe by the Food and Drug Administration. Previously reported studies have suggested that the ip LD50 of BHA may be as much as 2 orders of magnitude lower than its oral LD50. Metabolic activation of BHA to reactive intermediates possibly may be responsible for this result and may be related to other reported toxic effects. BHT has been reported to cause haemorrhagic lung damage and possible hepatocarcinogenicity in test animals. The present studies report investigations by electron spin resonance spectroscopy of free radical metabolites of BHA, BHT and related compounds. The primary, unstable phenoxy free radical of BHA has been generated by oxidation with horseradish peroxidase and hydrogen peroxide and detected by ESR spectroscopy. A scheme has been proposed for the peroxidatic oxidation of BHA. The ESR spectrum of the di-BHA dimer, one product of BHA oxidation, has been observed, analyzed, and reported. ESR studies have been extended to other phenol derivatives structurally related to BHA and suspected to be substrates for peroxidase. Similarly it has been found that BHT and structurally related phenols are substrates for peroxidation by horseradish peroxidase and hydrogen peroxide. In agreement with previous chemical and biochemical studies, it has been found that ortho-disubstituted phenols are oxidized to more stable phenoxy radicals than are ortho-monosubstituted phenols. The ESR hyperfine coupling constants for the phenoxy radicals studied are in agreement with those for similar radicals produced by chemical oxidation. Attention has been drawn to the biochemical and toxicological implications of these and related studies of BHA and BHT peroxidation.

UI	MeSH Term	Description	Entries
D010544	Peroxidases		Ovoperoxidase
D010636	Phenols	Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D002084	Butylated Hydroxytoluene	A di-tert-butyl PHENOL with antioxidant properties.	Butylhydroxytoluene,2,6-Bis(1,1-dimethylethyl)-4-methylphenol,2,6-Di-t-butyl-4-methylphenol,2,6-Di-tert-butyl-4-methylphenol,2,6-Di-tert-butyl-p-cresol,4-Methyl-2,6-ditertbutylphenol,BHT,Di-tert-butyl-methylphenol,Dibunol,Ionol,Ionol (BHT),2,6 Di t butyl 4 methylphenol,2,6 Di tert butyl 4 methylphenol,2,6 Di tert butyl p cresol,4 Methyl 2,6 ditertbutylphenol,Di tert butyl methylphenol,Hydroxytoluene, Butylated
D004578	Electron Spin Resonance Spectroscopy	A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.	ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
D006735	Horseradish Peroxidase	An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology.	Alpha-Peroxidase,Ferrihorseradish Peroxidase,Horseradish Peroxidase II,Horseradish Peroxidase III,Alpha Peroxidase,II, Horseradish Peroxidase,III, Horseradish Peroxidase,Peroxidase II, Horseradish,Peroxidase III, Horseradish,Peroxidase, Ferrihorseradish,Peroxidase, Horseradish
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships