Elevation of molybdenum hydroxylase levels in rabbit liver after ingestion of phthalazine or its hydroxylated metabolite

Johnson, C.; Stubley-Beedham, C.; Stell, J. G. P.

doi:10.1016/0006-2952(84)90159-x

Cited by 42 publications

(20 citation statements)

References 19 publications

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“…Oral administration of phthalazine or 1-hydroxyphthalazine to female rabbits causes an increase in the specific activity of liver aldehyde oxidase and XOR [156]. Intraperitoneal injection of the alkylating agents Nmethyl-N'-nitro-N-nitrosoguanidine, N-methyl-N-nitrosourea and methyl methanesulfonate (MMS) into rats also causes an induction of liver aldehyde oxidase [157].…”

Section: Gender and Sex Hormonesmentioning

confidence: 99%

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Garattini

Fratelli

Terao

2007

Cell. Mol. Life Sci.

166

184

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Mammalian aldehyde oxidases are a small group of proteins belonging to the larger family of molybdo-flavoenzymes along with xanthine oxidoreductase and other bacterial enzymes. The two general types of reactions catalyzed by aldehyde oxidases are the hydroxylation of heterocycles and the oxidation of aldehydes into the corresponding carboxylic acids. Different animal species are characterized by a different complement of aldehyde oxidase genes. Humans contain a single active gene, while marsupials and rodents are characterized by four such genes clustering at a short distance on the same chromosome. At present, little is known about the physiological relevance of aldehyde oxidases in humans and other mammals, although these enzymes are known to play a role in the metabolism of drugs and compounds of toxicological importance in the liver. The present article provides an overview of the current knowledge of genetics, evolution, structure, enzymology, tissue distribution and regulation of mammalian aldehyde oxidases.

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Section: Gender and Sex Hormonesmentioning

confidence: 99%

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Garattini

Fratelli

Terao

2007

Cell. Mol. Life Sci.

166

184

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“…Partially purified rabbit aldehyde oxidase was prepared according to a previously reported procedure (Johnson et al 1984). Briefly, aliquots of rabbit liver S9 fractions purchased from Xenotech were heated to 55-60 C for 10 minutes, then cooled on wet ice and centrifuged at 10 000 Â g for 30 minutes at 5 C. The supernatant was filtered through glass wool and sufficient solution of saturated ammonium sulfate was added to give a 50% saturated solution.…”

Section: Preparation Of Rabbit Aldehyde Oxidasementioning

confidence: 99%

Characterization of benzimidazole and other oxidative and conjugative metabolites of brimonidinein vitroand in ratsin vivousing on-line H/D exchange LC-MS/MS and stable-isotope tracer techniques

Rowe

Heidelbaugh

et al. 2007

Xenobiotica

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The characterization of brimonidine metabolites presents some challenges since brimonidine and its metabolites generate few structurally informative fragment ions in the LC-MS/MS spectra. The objective of the current study is to use on-line hydrogen/deuterium (H/D) exchange LC-MS/MS and stable-isotope tracer techniques to further characterize unknown brimonidine metabolites in vitro and in vivo. Brimonidine and D4-brimonidine were co-incubated in rat and human microsomes and rabbit aldehyde oxidase in vitro. In addition, the urine was collected from rats co-administered orally with brimonidine and D4-brimonidine. The hepatic microsomal and urinary metabolites were then characterized by H/D LC-MS/MS system. In addition to previously characterized 2-oxobrimonidine, 3-oxobrimonidine and 2,3-dioxobrimonidine, the results show that oxidation occurs at quinoxaline ring producing oxo-hydroxybrimonidine and hydroxyquinoxaline metabolites. The hydroxyquinoxaline metabolite was only observed in microsomal incubations with hydroxylation at the 7- or 8- position. The dehydro-hydroxybrimonidine metabolites were characterized as 2-oxo or 3-oxo -4', 5'-dehydrobrimonidine. A novel metabolite ((4-bromo-lH-benzoimidazol-5-yl)-imidazolidin-2-ylidene-amine) of benzimidazole derivative of brimonidine in rats in vivo was identified and confirmed with reference standard. In conclusion, on-line H/D exchange LC-MS/MS and stable-isotope tracer techniques are useful for the characterization of brimonidine metabolites.

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“…It has been shown that testosterone induced both aldehyde oxidase and xanthine oxidase in mice and rats [16][17][18] . The activity of molybdenum hydroxylases was shown to increase in rabbit liver using phthalazine or 1-phthalazinone [9] .…”

Section: Aldehyde Oxidase and Xanthine Oxidase Activitiesmentioning

confidence: 99%

“…The activity of partially purified aldehyde oxidase was determined spectrophotometrically at 420 nm using the method described by Johnson et al [9] with both phthalazine (1 mM) and 3-methylisoquinoline (1 mM). The activity of xanthine oxidase was estimated with xanthine (50 µM) at 295 nm [8,12] .…”

Section: Enzyme Assaysmentioning

confidence: 99%

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Activity Changes of Molybdenum Hydroxylases in Liver, Kidney and Jejunum of Streptozotocin - Induced Diabetic Rats

Al-Bar¹

2005

sci

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ABSTRACT. The aim of this study is to investigate the effect of diabetes induction on the specific activity of two molybdenum hydroxylases, namely aldehyde oxidase and xanthine oxidase. Streptozotocin in a single i.p. injection (65 mg/kg) induced diabetes in male Wistar rats as indicated by a sharp and significant increase of plasma glucose level after 5 days of the treatment. Three tissues (liver, kidney and jejunum) were excised and assayed for the activity of aldehyde oxidase and xanthine oxidase. Two substrates (phthalazine and 3-methylisoquinoline) were used to measure aldehyde oxidase activity, while xanthine was used for xanthine oxidase. Hepatic aldehyde oxidase activity was increased significantly (P < 0.025) in diabetic rats as compared to controls when phthalazine was used as a substrate. The other two tissues (kidney, jejunum) did not show any significant variation in aldehyde oxidase activity when diabetic and control rats were compared. No significant change of this enzymic activity was noted in the three tissues (liver, kidney and jejunum) when 3-methylisoquinoline was used as a substrate. On the other hand, xanthine oxidase activity in liver and jejunum was markedly decreased (P < 0.005 and P < 0.0005, respectively) in diabetic rats while the enzymic activity of kidney remained unchanged. These results suggest the presence of multiple isomeric forms of molybdenum hydroxylases and some of these forms can be induced or suppressed by the diabetic inducing agent streptozotocin.

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Elevation of molybdenum hydroxylase levels in rabbit liver after ingestion of phthalazine or its hydroxylated metabolite

Cited by 42 publications

References 19 publications

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Mammalian aldehyde oxidases: genetics, evolution and biochemistry

Characterization of benzimidazole and other oxidative and conjugative metabolites of brimonidinein vitroand in ratsin vivousing on-line H/D exchange LC-MS/MS and stable-isotope tracer techniques

Activity Changes of Molybdenum Hydroxylases in Liver, Kidney and Jejunum of Streptozotocin - Induced Diabetic Rats

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