Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver

J. B. Watkins, C. D. Klaassen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Since many xenobiotics alter hepatic UDP-glucuronosyltransferase activity, their effect on UDPGA concentration was determined. Rats were pretreated with: 1) microsomal enzyme inducers (7,8-benzoflavone, benzo(a)pyrene, butylated hydroxyanisole, isosafrole, 3-methylcholanthrene, phenobarbital, pregnenolone-16α-carbonitrile (PCN), 2,3,7,8-tetrachlorodibenzo-p-dioxin, trans-stilbene oxide); 2) inhibitors of microsomal enzymes (cobaltous chloride, piperonylbutoxide, SKF 525-A, borneol, galactosamine); 3) hepatotoxins (allyl alcohol, aflatoxin B1, α-naphthylisothiocyanate, bromobenzene, cadmium chloride, carbon tetrachloride, 1,1-dichloroethylene), and 4) commonly used anesthetics (pentobarbital, urethane, diethyl ether, halothane, enflurane, methoxyflurane). Rats were decapitated before removal of the liver. All inducers except PCN and isosafrole increased UDPGA 36-85% above control. Mixed-function oxidase inhibitors had no effect whereas borneol and galactosamine reduced UDPGA 85-90%. Aflatoxin B1 and cadmium produced decreases of 59 and 25%, respectively. Hepatic UDPGA content was diminished 70-95% after exposure to the inhalation anesthetics, whereas the other anesthetics reduced UDPGA about 25%. Thus, numerous xenobiotics alter the concentration of UDPGA in rat liver, which may influence the rate of glucoronidation.

Original languageEnglish (US)
Pages (from-to)37-40
Number of pages4
JournalDrug Metabolism and Disposition
Volume11
Issue number1
StatePublished - 1983
Externally publishedYes

Fingerprint

Uridine Diphosphate Glucuronic Acid
Liver
Rats
Pregnenolone Carbonitrile
Galactosamine
Aflatoxin B1
Xenobiotics
Anesthetics
Methoxyflurane
Proadifen
Butylated Hydroxyanisole
Inhalation Anesthetics
Cadmium Chloride
Enflurane
Glucuronosyltransferase
Methylcholanthrene
Carbon Tetrachloride
Benzo(a)pyrene
Urethane
Enzyme Inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver. / Watkins, J. B.; Klaassen, C. D.

In: Drug Metabolism and Disposition, Vol. 11, No. 1, 1983, p. 37-40.

Research output: Contribution to journalArticle

Watkins, J. B. ; Klaassen, C. D. / Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver. In: Drug Metabolism and Disposition. 1983 ; Vol. 11, No. 1. pp. 37-40.
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