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Modifications of drug metabolism by disulfiram and diethyldithiocarbamate II.d-glucuronic acid pathway

Authors
Journal
Chemico-Biological Interactions
0009-2797
Publisher
Elsevier
Publication Date
Volume
15
Issue
3
Identifiers
DOI: 10.1016/0009-2797(76)90153-8
Disciplines
  • Biology

Abstract

Abstract Hepatic enzymes connected with the formation and metabolism of free d-glucuronic acid were affected in rats after treatment with disulfiram or diethyldithiocarbamate (300 mg/kg, intragastrically, per day, 4 X). The activities of UDPglucose dehydrogenase, UDPglucuronic acid pyrophosphatase, UDPglucuronosyltransferase and l-gulonate dehydrogenase were enhanced, while those of glucose-6-phosphate dehydrogenase, β-glucuronidase and d-glucuronolactone dehydrogenase were inhibited. These changes were more pronounced with disulfiram than diethyldithiocarbamate. Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyltransferase, but brought about different effects on the other enzymes. Concurrent administration of phenobarbital with disulfiram or diethyldithiocarbamate led to potentiation or antagonism of the primary effects of each compound when given alone. The results suggest that activation of the d-glucuronic acid pathway may proceed in various ways, and that it is not necessarily followed by a simultaneous induction of the microsomal mixed-function oxygenase activity.

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