Biochemical studies of toxic agents. 3. The isolation of 1- and 2-naphthylsulphuric acid and 1- and 2-naphthylglucuronide from the urine of rats dosed with 1- and 2-naphthol

Berenbom, Max; Young, L.

doi:10.1042/bj0490165

Cited by 51 publications

(13 citation statements)

References 6 publications

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“…1-NT has been reported to be metabolized only by glu curonidation and sulfation [28], In agree ment with this, no other metabolites were found in the present study. The possibility was investigated that the lung might possess high levels of (3-glucuronidase and/or sulfa tase which could hydrolyze the correspond ing conjugates.…”

Section: Discussionsupporting

confidence: 82%

Glucuronidation and Sulfation in Subcellular Fractions and in the Isolated Perfused Rabbit Lung: Influence of Ethanol

Yang

Carlson²

1991

Pharmacology

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Glucuronidation and sulfation of 1-naphthol, 7-hydroxycoumarin, 4-nitrocatechol and phenolphthalein were studied in rabbit lung and liver. Pulmonary UDP-glucuronyltransferase and sulfotransferase activities in subcellular fractions were approximately 20–50% of those determined in the liver. Ethanol did not markedly induce these enzymes in either tissue. Glucuronidation and sulfation of 1-naphthol and 7-hydroxycoumarin were also studied in the isolated perfused rabbit lung as an intact cell model. Neither glucuronidation nor sulfation of 1-naphthol was observed. The absence of conjugate formation was due neither to the presence of β-glucuronidase and/or sulfatase, nor to alternative biotransformation pathways. About 35% of the initial 7-hydroxycoumarin was conjugated, the majority being sulfate conjugate (14.4 nmol/h) with only minor amounts (0.12%) of the glucuronide. These results indicate the importance of studying both whole organ and in vitro metabolism.

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Section: Discussionsupporting

confidence: 82%

Glucuronidation and Sulfation in Subcellular Fractions and in the Isolated Perfused Rabbit Lung: Influence of Ethanol

Yang

Carlson²

1991

Pharmacology

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“…There is an increase in glucuronide formation when the naphthol concentration in the perfusion medium is increased from 0.2 to 0.5 mM, but higher concentrations do not significantly increase this rate. There are only two major routes of naphthol metabolism: glucuronidation and sulfate ester formation [13]. Thus, a balance sheet of the metabolites can be determined.…”

Section: Discussionmentioning

confidence: 99%

UDP‐glucuronyltransferase in Perfused Rat Liver and in Microsomes: Influence of Phenobarbital and 3‐Methylcholanthrene

Bock

White

1974

European Journal of Biochemistry

169

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Liver microsomal UDP-glucuronyltransferase (l-naphthol as substrate) is activated about 10-fold by treatment of native microsomes in vitro with Triton X-100. Following pretreatment of rats with 3-methylcholanthrene or phenobarbital the specific activities of detergent-activated microsomes were increased by about 300 % and 40 %, respectively, while the corresponding increases in native microsomes were only about 70 % and 10 %, respectively .In isolated liver perfused with 0.5 mM l-naphthol, the rate of glururonidation of naphthol, as determined by the appearance of naphthol glucuronide in the perfusate, bile and liver tissue, was 0.1 pmol x min-1 x g liver-1. This rate of glucuronidation was increased by 70% in rats pretreated with 3-methylcholanthrene and by 140% following phenobarbital treatment, in contrast to the changes observed in microsomes.A UDP-glucuronic acid level of 0.3 pmol/g liver was determined in perfused liver from control rats. This level remained unchanged during perfusion with 0.5 mM l-naphthol. In the perfused liver from phenobarbital or 3-methylcholanthrene-treated rats, the UDP-glucuronate level increased to 0.5 pmol/g liver.In control, 3-methylcholanthrene or phenobarbital-treated rats, rates of glucuronidation of 1-naphthol in the perfused liver system correspond best with the UDP-glucuronyltransferase activities determined in native microsomes when the different UDP-glucuronate levels, microsomal protein contents and liver weights are taken into account.The results suggest that the enzyme is mostly latent in the microsomal membrane and that this latency is increased after pretreatment of rats with 3-methylcholanthrene despite the marked enzyme induction.Liver microsomal UDP-glucuronyltransferase can be markedly affected by a variety of treatments altering membrane structure, e.g. an about 10-fold activation is observed in vitro after the addition of detergents to native microsomes [l-51. It is therefore of considerable interest to establish the enzyme activity in intact cells in vivo. This has important pharmacological implications since a wide range of endogenous and exogenous compounds including many drugs and their metabolites are inactivated by this enzyme.There is accumulating evidence that UDP-glucuronyltransferase consists of a number of related enzymes with different substrate specificities [5 -71. These can be selectively induced by different types of inducing Enzyme. UDP-glucuronyltransferase or UDP-glucuronate glucuronyltransferase (acceptor unspecific) (EC 2.4. 1.17). Since the number of substrate-specific forms of this enzyme is uncertain, in this paper UDP-glucuronyltransferase refers only to the enzyme catalyzing the glucuronidation of l-naphthol.compounds, e.g. phenobarbital treatment of rats induces the glucuronidation of chloramphenicol and bilirubin whereas pretreatment of the animals with 3-methylcholanthrene induces the glucuronidation of 1-naphthol and p-nitrophenol [5]. So far, the induction of these enzymes can be best measured in their maximally activated form si...

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“…The product had the R. of 1-naphthol, suggesting that the original radioactivity was probably present as 1:2-dihydro-1:2-dihydroxynaphthalene (Young, 1947). In agreement with Berenbom & Young (1951) and Boyland & Wiltshire (1953), the diol could not be detected in the urine of rats treated with l-naphthol.…”

Section: Resultsmentioning

confidence: 75%

“…Berenbom & Young (1951) and Boyland & Wiltshire (1953) have concluded that rats and rabbits receiving 1-naphthol produce 1-naphthol, 1-naphthyl sulphate and 1-naphthyl glucosiduronic acid. Two of the additional metabolites which we have found in rats, 1:2-dihydro-2-hydroxy-1naphthyl glucosiduronic acid and 1-naphthylmercapturic acid, may be the result of conjugations involving 1:2-dihydro-1:2-dihydroxynaphthalene, which has not been identified as a product of 1-naphthol metabolism in rats.…”

Section: Discussionmentioning

confidence: 99%

“…1:2-Dihydro-2-hydroxy-1-naphthyl glucosiduronic acid, N-acetyl-S-(1:2-dihydro-2-hydroxynaphthyl)cysteine (1-naphthylpremercapturic acid), 2-hydroxy-l-naphthyl sulphate and N-acetyl-S-(1-naphthyl)cysteine (1-naphthylmercapturic acid) were kindly supplied by Professor E. Boyland. 1:2-Dihydro-1:2-dihydroxynaphthalene was isolated from rat urine by the method of Corner & Young (1955) and 1-naphthyl glucosiduronic acid by the method of Berenbom & Young (1951). 1-Naphthyl sulphate was synthesized by the method of Feigenbaum & Neuberg (1941).…”

Section: Methodsmentioning

confidence: 99%

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The metabolism of naphthalene and 1-naphthol by houseflies and rats

Terriere

Boose

Roubal

1961

Biochemical Journal

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Biochemical studies of toxic agents. 3. The isolation of 1- and 2-naphthylsulphuric acid and 1- and 2-naphthylglucuronide from the urine of rats dosed with 1- and 2-naphthol

Cited by 51 publications

References 6 publications

Glucuronidation and Sulfation in Subcellular Fractions and in the Isolated Perfused Rabbit Lung: Influence of Ethanol

Glucuronidation and Sulfation in Subcellular Fractions and in the Isolated Perfused Rabbit Lung: Influence of Ethanol

UDP‐glucuronyltransferase in Perfused Rat Liver and in Microsomes: Influence of Phenobarbital and 3‐Methylcholanthrene

The metabolism of naphthalene and 1-naphthol by houseflies and rats

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