Further studies of metyrapone effects upon anilide hydroxylation.

Details

• Personal Author:
  Leibman KC ; Ortiz E
• Description:
  Procedures for the determination of phenolic products, and the effects of metyrapone (54364) and related compounds on anilide hydroxylation were investigated. Adult male Holtzman-rats and New- Zealand-White-rabbits, pretreated for 3 days with sodium- phenobarbital (57307), were used for preparation and reconstitution of lyophilized liver fractions. The formation of acetaminophen (103902) from acetanilide (103844) in rat and rabbit liver homogenate was demonstrated by gas chromatography of extracts of incubation mixtures. Hydrolysis of acetaminophen was minimally inhibited by an 0.4 millimolar concentration of metyrapone in rat and rabbit liver preparations. The formation of acetaminophen from acetanilide was enhanced 2 fold in rat liver homogenate in the presence of an 0.4 millimolar concentration of metyrapone; the production of p-aminophenol (123308) was not affected. In rabbit liver, the formation of acetaminophen was inhibited by 80 percent by an 0.4 millimolar concentration of metyrapone. Para-aminophenol production from the homologous series of formanilide (103708), acetanilide and propionanilide (620713) was greatest from formanilide and least from propionanilide. While the hydroxylation of acetanilide in the rat liver preparation was enhanced with a maximum at an 0.4 millimolar concentration of metyrapone, the hydroxylation of other anilides was inhibited. Alpha,alpha'- dipyridyl (366187) enhanced phenol production from carbonacylanilides but did not affect phenol production from methane- sulfonanilide (1197224). The authors conclude that this indicates that the mechanism of enhancement of anilide hydroxylation by these modifiers is different. [Description provided by NIOSH]
• Subjects:
  Animals Biological Assay Chemistry Energy Metabolism Enzymes Occupational Health Phenol Safety
• Keywords:
  NIOSH-Publication; NIOSH-Grant; Grants-other; Animal-studies; Liver-cells; Chemical-properties; Bioassays; Dose-response; Metabolic-study; Enzyme-activity; Biosynthesis; Phenolic-compounds
• ISSN:
  0090-9556
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Florida ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  3
• Issue:
  6
• NIOSHTIC Number:
  nn:00131576
• Citation:
  Drug Metab Dispos 1975 Nov-Dec; 3(6):507-512
• Contact Point Address:
  Pharmacology and Therapeutics Univ of Florida Coll of Med Dept of Pharma & Therapeutics Gainesville, Fla 32601
• CAS Registry Number:
  2,2′-Bipyridine (CAS RN 366-18-7) ; 4-Aminophenol (CAS RN 123-30-8) ; Acetaminophen (CAS RN 103-90-2) ; Acetanilide (CAS RN 103-84-4) ; Formanilide (CAS RN 103-70-8) ; Metyrapone (CAS RN 54-36-4) ; N-Phenylmethanesulfonamide (CAS RN 1197-22-4) ; N-Phenylpropanamide (CAS RN 620-71-3) ; Phenobarbital sodium (CAS RN 57-30-7)
• Federal Fiscal Year:
  1976
• NORA Priority Area:
  Other Occupational Concerns ; Grants Other
• Performing Organization:
  University of Florida Gainesville, Gainesville, Florida
• Peer Reviewed:
  True
• Start Date:
  19710101
• Source Full Name:
  Drug Metabolism and Disposition
• End Date:
  19841130
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247528/cdc_247528_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]