Metabolism of polycyclic compounds. 17. The reaction of 1:2-dihydronaphthalene and 1:2-epoxy-1:2:3:4-tetrahydronaphthalene with glutathione catalysed by tissue preparations

Booth, Joan; Boyland, E.; Sato, Tamio; Sims, P.

doi:10.1042/bj0770182

Cited by 70 publications

(12 citation statements)

References 12 publications

(4 reference statements)

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“…According to the current view, the epoxides are then converted nonenzymatically to phenols or enzymatically to their GSH conjugates and dihydrodiol derivatives (15,16). Subsequently, the GSH conjugates are transformed and excreted in urine as premercapturic acids while the dihydrodiol derivatives are converted to catechols.…”

Section: Histologic Studiesmentioning

confidence: 99%

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Brodie

Reid

Cho

et al. 1971

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

322

124

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Treatment of rats with phenobarbital, which stimulates the activity of the drug-metabolizing enzymes in the liver, potentiates hepatic necrosis elicited by bromobenzene and a number of other chemically inert halogenated aromatic hydrocarbons. Radioautographic studies indicate that ['4Clbromobenzene is covalently bound at the sites of necrosis. From these results, it is inferred that the hepatotoxic effects of the halogenated aromatic hydrocarbons are mediated by chemically active metabolites formed in hepatocytes. In accord with this view, a number of aromatic halogenated hydrocarbons are converted by microsomes in vitro to active intermediates which form covalent complexes with glutathione (GSH).

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Section: Histologic Studiesmentioning

confidence: 99%

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Brodie

Reid

Cho

et al. 1971

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

322

124

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“…As early as 1950 Eric Boyland (75) in England had proposed the formation of epoxides of aromatic compounds, which he inferred from the finding of 1,2-dihydronaphthalene-1,2-diol in urine of animals dosed with naphthalene. In 1960 Joan Booth et al (76) in Boyland's laboratory found that 1,2-dihydronaphthalene and 1,2,3,4-tetrahydronaphthalene 1,2-oxide were converted to the same glutathione metabolite when they were incubated with glutathione and either rat liver slices or microsomes. In 1967, Jordan Holtzman et al (77) in LCP found that only one of the oxygen atoms in the 1,2-dihydronaphthalene 1,2-diol formed from naphthalene by mouse liver microsomes originated from atmospheric oxygen.…”

Section: Chemically Reactive Metabolitesmentioning

confidence: 98%

Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, NIH: A Short History

Gillette¹

2000

Annu. Rev. Pharmacol. Toxicol.

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Two analogs of phenylbutazone, labelled G-25671 and 6-28315, have been shown to have potent uricosuric effects. This report concerns the therapeutic properties in 44 patients of 6-28315, which is a sulfoxide metabolite of G-25671. AI-though the effects of this agent compared favorably with probenecid, the periods of administration were not sufficiently long to exclude toxicity. Duo analogos de phenylbutazona, iden-tificate como G-25671 e G-28315, se ha monstrate potente como agentes uricosuric. Le presente reporto con-ceme le proprietates therapeutic de G-28315 (un metabolito sulfoxydic de G-25671), observate in essayos con 44 patientes. Ben que le effectos esseva comparabile a illos de probenecido, le cursos de administration non esseva satis extense pro excluder toxicitate. HE PLACE of probenecid as a uricosuric agent suitable for protracted T use in the prevention and treatment of chronic gouty arthritis is now well established. There are, however, limitations to its effectiveness. Occasionally probenecid is not well tolerated and cannot be administered in effective dosage unless prior "desensitization" is possible; in our series drug rash occurred in 5 per cent and marked gastric distress in 8 per cent of 169 cases,l necessitating discontinuance of the drug in some instances. Probenecid has no "antirheu-matic" properties, hence does not relieve multiple joint stiffness and persistent joint pain associated with chronic gouty arthritis for the months required to mobilize urate depoists sufficiently. Even in daily dosage of two or three Gm., probenecid may fail to lower the serum urate to satisfactory levels, notably in patients with distinct renal damage. In our experience' the serum urate could not be maintained below 7 mg. per cent in 27 per cent of 186 protracted trials in 122 gouty subjects. In view of these limitations it would be desirable, at least in the speciaI circumstances indicated, to have alternative potent uricosuric drugs at hand. Of such drugs presently available, four have received special consideration: salicylate,2-5 zoxaz~larnine~~~ and the phenylbutazone analogs, G-25671 and the sulfoxide metabolite of G-25671, namely G-28315.A-1' The present communication is concerned with G-2831s (4-[phenylsulfoxyethyl]-l,2-diphenyl-3, 5-pyrazolidinedione) * and the results of its use in 44 gouty subjects.

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“…33 Although the PAHs were among the first carcinogens to be studied with regard to their biotransformation, the discovery of their active DNA-binding intermediates has taken quite a long time. Some 20-25 years after the first reports on urinary metabolites of anthracene 25 and DBlaMK 34 epoxides (arene oxides) were shown to be the intermediates, 35,36 and another 10 years passed until the first arene oxide intermediate was isolated. 37 In 1973, Borgen et al reported that a metabolite of B[a]P, the 7,8-dihydrodiol, binds to a 10-fold greater extent to DNA in vitro than its parent compound.…”

mentioning

confidence: 97%

Polycyclic Aromatic Hydrocarbon-Induced Carcinogenesis – An Introduction

Luch

2005

The Carcinogenic Effects of Polycyclic Aromatic Hydrocarbons

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Metabolism of polycyclic compounds. 17. The reaction of 1:2-dihydronaphthalene and 1:2-epoxy-1:2:3:4-tetrahydronaphthalene with glutathione catalysed by tissue preparations

Cited by 70 publications

References 12 publications

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, NIH: A Short History

Polycyclic Aromatic Hydrocarbon-Induced Carcinogenesis – An Introduction

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