Acetaminophen: enzymatic formation of a transient phenoxyl free radical

West, Paul R.; Harman, Laura S.; Josephy, P. David; Mason, Ronald P.

doi:10.1016/0006-2952(84)90222-3

Cited by 91 publications

(34 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Thompson et al suggested that oxidation of p-eugenol by horseradish peroxidase occurs via a one-electron pathway yielding a phenoxyl radical. 14) Similar observations were made for other phenolic compounds, such as phenol, 5) BHA, 15) acetaminophen, 16) quercetin 17) and 17b -estradiol. 6) Next, we investigated how phenolic compounds affect Eq.…”

Section: Resultssupporting

confidence: 70%

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Ueda¹,

Tsuchiya²,

Ozawa³

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Reactive oxygen species such as superoxide radicals (O 2 · Ϫ ), hydroxyl radicals, and singlet oxygen have been implicated both in the aging process and in degenerative disease. [1][2][3][4] Phenolic compounds are known to act as poisons under certain conditions. The mechanism of toxicity of phenolic compounds such as phenol 5) and 17b -estradiol 6) is suggested to be the generation of O 2 · Ϫ during the reaction of the compounds with oxidative enzymes (peroxidases, tyrosinase, prostaglandin synthase, etc.) in the presence of biological reductants such as reduced b -nicotinamide adenine dinucleotide (NADH), reduced b -nicotinamide adenine dinucleotide phosphate (NADPH) or glutathione (GSH). On the other hand, phenolic compounds that scavenge O 2 · Ϫ may be of potential therapeutic use as antioxidants. 7,8) In consideration of these points, we are interested in elucidating how phenolic compounds can enhance the generation of O 2 · Ϫ from the reaction of lactoperoxidase (LPO) with NAD(P)H and GSH, and whether there is a relationship between the enhancing activity of the phenolic compounds and their electrochemical properties. LPO is a mammalian hemoprotein found in saliva, tears, and milk, and forms part of the antimicrobial defense system. As the electrochemical data for phenolic compounds have been obtained under a wide range of experimental conditions, however, it is difficult to make direct comparisons. Thus, the ability of a phenolic compound to scavenge a stable radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), was used in this study to assess the electrochemical properties of the compounds. 1,1-Diphenyl-2-picrylhydrazyl is a radical widely used for the rough estimation of the antioxidant activity of phenolic compounds. The ability of a phenolic compound to scavenge DPPH is recently suggested to be related to the redox potential.9) The chemical structure of the nineteen phenolic compounds used in this study are depicted in Fig. 1. The compounds are 17b -estradiol, phenol, p-chlorophenol, p-eugenol, isoeugenol, 3,4-dimethylphenol, quercetin, Trolox C, diethylstilbestrol, bisphenol A, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, acetaminophen, guaiacol, p-methoxyphenol, curcumin, 2-hydroxyestradiol, gallic acid, and 3(2)-tert-butyl-4-hydroxyanisole. Phenolic dental medicaments including phenol, pchlorophenol, p-eugenol, isoeugenol, and guaiacol have been used for disinfection and sedative treatment for pulpitis in dental practice.10) We report here that the ability of phenolic compounds to enhance the LPO/H 2 O 2 -catalyzed oxidation of NAD(P)H or GSH is in inverse proportion to their quenching activity against the DPPH. Materials and MethodsMaterials 17b -Estradiol was purchased from Steraloids Inc. (U.S.A.). p-Chlorophenol, diethylstilbestrol (DES), reduced b -nicotinamide adenine dinucleotide (NADH), lactoperoxidase (LPO), catalase, superoxide dismutase (SOD), and reduced glutathione (GSH) were purchased from Sigma Chemical Co. (U.S.A.). Trolox ® (abbreviated as Trolox C hereinafter) was obtained fro...

show abstract

Section: Resultssupporting

confidence: 70%

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Ueda¹,

Tsuchiya²,

Ozawa³

2001

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…Reduction of the protoporphyrin radical cation would prevent the formation of the tyrosyl radical. There is abundant evidence that ApAP and other reductants act to reduce this higher oxidative state of the PGHS-peroxidase and other peroxidases to the ferric or ''resting'' state, a process in which ApAP serves as a cosubstrate for the peroxidases (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). By contrast, ibuprofen, indomethacin, and flurbiprofen, inhibitors that block access of substrate to the PGHS-cyclooxygenase catalytic site, do not act as cosubstrates of the PGHS-peroxidase (28).…”

Section: Discussionmentioning

confidence: 99%

“…After finding that the action of ApAP in HUVECs is to inhibit the PGHSs, the determinants of the selectivity of this inhibition for endothelial cells were investigated. The basis for these investigations was derived from the accumulating evidence that ApAP inhibits the PGHSs by reducing the higher oxidation state of the enzymes (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). The PGHS-peroxidase, by reduction of a hydroperoxide to its alcohol, oxidizes the enzyme from its resting state (ferric heme) to the ferryloxo-protoporphyrin radical cation, which by intramolecular electron transfer generates the tyrosyl radical in the PGHS-cyclooxygenase site that is required for oxygenation of arachidonic acid (AA) (35)(36)(37)(38).…”

mentioning

confidence: 99%

Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H ₂ synthases

Boutaud

Aronoff

Richardson

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

207

204

View full text Add to dashboard Cite

“…All experiments were done at room temperature. Fast-flow ESR experiments which detected the tyrosyl radical were done using a TM 110 resonator equipped with a 17-mm quartz, mixing flat cell (ϳ225-l volume) designed for fast-flow measurements (Wilmad, NJ) (14). This mixing flat cell had a post-mixing dead volume of approximately 300 l, which, when flowing at 60 ml/min, resulted in a post-mixing observation time of approximately 300 ms. Fast-flow ESR measurements of the ascorbate radical were done using a Bruker dielectric mixing resonator with a 1-l active volume.…”

Section: Methodsmentioning

confidence: 99%

The Fate of the Oxidizing Tyrosyl Radical in the Presence of Glutathione and Ascorbate

Sturgeon

Sipe

Barr

et al. 1998

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cellular systems contain as much as millimolar concentrations of both ascorbate and GSH, although the GSH concentration is often 10-fold that of ascorbate. It has been proposed that GSH and superoxide dismutase (SOD) act in a concerted effort to eliminate biologically generated radicals. The tyrosyl radical (Tyr ⅐ ) generated by horseradish peroxidase in the presence of hydrogen peroxide can react with GSH to form the glutathione thiyl radical (GS ⅐ ). GS ⅐ can react with the glutathione anion (GS ؊ ) to form the disulfide radical anion (GSSG . ). This highly reactive disulfide radical anion will reduce molecular oxygen, forming superoxide and glutathione disulfide (GSSG). In a concerted effort, SOD will catalyze the dismutation of superoxide, resulting in the elimination of the radical. The physiological relevance of this GSH/SOD concerted effort is questionable. In a tyrosyl radical-generating system containing ascorbate (100 M) and GSH (8 mM), the ascorbate nearly eliminated oxygen consumption and diminished GS ⅐ formation. In the presence of ascorbate, the tyrosyl radical will oxidize ascorbate to form the ascorbate radical. When measuring the ascorbate radical directly using fast-flow electron spin resonance, only minor changes in the ascorbate radical electron spin resonance signal intensity occurred in the presence of GSH. These results indicate that in the presence of physiological concentrations of ascorbate and GSH, GSH is not involved in the detoxification pathway of oxidizing free radicals formed by peroxidases.

show abstract

Acetaminophen: enzymatic formation of a transient phenoxyl free radical

Cited by 91 publications

References 12 publications

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H ₂ synthases

The Fate of the Oxidizing Tyrosyl Radical in the Presence of Glutathione and Ascorbate

Contact Info

Product

Resources

About

Acetaminophen: enzymatic formation of a transient phenoxyl free radical

Cited by 91 publications

References 12 publications

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Relationship between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-Catalyzed Oxidation of NAD(P)H or GSH and their DPPH Scavenging Ability.

Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H 2 synthases

The Fate of the Oxidizing Tyrosyl Radical in the Presence of Glutathione and Ascorbate

Contact Info

Product

Resources

About

Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H ₂ synthases