title: Recombinant human diamine oxidase activity is not inhibited by ethanol, acetaldehyde, disulfiram, diethyldithiocarbamate or cyanamide.
abstract: Human diamine oxidase (hDAO, EC 1.4.3.22) is the key enzyme in the degradation of extracellular histamine. Consumption of alcohol is a known trigger of mast cell degranulation in patients with mast cell activation syndrome. Ethanol may also interfere with enzymatic histamine degradation, but reports on the effects on DAO activity are controversial. There are also conflicting reports whether disulfiram, an FDA-approved agent in the treatment of alcohol dependence, inhibits DAO. We therefore investigated the inhibitory potential of ethanol and disulfiram and their metabolites on recombinant human DAO (rhDAO) in three different assay systems. Relevant concentrations of ethanol, acetaldehyde, and acetate did not inhibit rhDAO activity in an in vitro assay system using horseradish peroxidase (HRP) -mediated luminol oxidation. The aldehyde dehydrogenase (ALDH; EC 1.2.1.3) inhibitors cyanamide and its dimer dicyanamide also had no effect on DAO activity. In one assay system, the irreversible ALDH inhibitor disulfiram and its main metabolite diethyldithiocarbamate seemed to inhibit DAO activity. However, the decreased product formation was not due to a direct block of DAO activity but resulted from inhibition of peroxidase employed in the coupled system. Our in vitro data do not support a direct blocking effect of ethanol, disulfiram, and their metabolites on DAO activity in vivo.
authors.affiliation: Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Bartko
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gludovacz
authors.affiliation: Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Petroczi
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
authors.affiliation: Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria. Electronic address: bernd.jilma@meduniwien.ac.at.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D003412:Cricetulus; D003484:Cyanamide / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D000431:Ethanol; D003484:Cyanamide; D004050:Ditiocarb; D006631:Amine Oxidase (Copper-Containing); D000079:Acetaldehyde; D004221:Disulfiram
keywords: Alcohol deterrents; Ethanol and metabolites; Histamine toxicity; Human diamine oxidase; Inhibition of enzymatic activity