HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria.

Abstract
1. The hypothesis that uroporphyria-inducing drugs stimulate the oxidation of uroporphyrinogen by a microsomal NADPH-dependent mechanism was tested. 2. 3,4,3',4'-Tetrachlorobiphenyl, a very effective inducer of uroporphyria in chick-embryo hepatocyte cultures, stimulates the NADPH-dependent oxidation of uroporphyrinogen by chick-embryo microsomal fraction in vitro. 3. Two different actions of 3,4,3',4'-tetrachlorobiphenyl are apparently required for this effect: (a) induction of a microsomal system by treatment in vivo and (b) interaction with the induced microsomal fraction in vitro, producing an oxidizing species. 4. The analogue 2,4,2',4'-tetrachlorobiphenyl is relatively ineffective in both the production of porphyria in culture and the stimulation of porphyrinogen oxidation in vitro. 5. Rat hepatocytes do not develop uroporphyria when treated with polychlorinated biphenyls in culture, yet they respond to these drugs with typical induction of cytochrome P-448-dependent drug metabolism. 6. These data provide support for the hypothesis of an increased oxidation of uroporphyrinogen in drug-induced uroporphyria, but also suggest that induction of cytochrome P-448 is not the only factor involved. 7. Both I and III isomers of uroporphyrin and heptacarboxylate porphyrin accumulate when chicken hepatocytes are made uroporphyric by drugs; treatment with desferrioxamine causes a marked decrease in both isomers, suggesting that iron may be involved in the accumulation of both.
AuthorsF De Matteis, C Harvey, C Reed, R Hempenius
JournalThe Biochemical journal (Biochem J) Vol. 250 Issue 1 Pg. 161-9 (Feb 15 1988) ISSN: 0264-6021 [Print] England
PMID3128275 (Publication Type: Journal Article)
Chemical References
  • Benzoflavones
  • Porphyrinogens
  • Porphyrins
  • Uroporphyrinogens
  • 2,4,2',4'-tetrachlorobiphenyl
  • alpha-naphthoflavone
  • Aminolevulinic Acid
  • Cytochrome P-450 Enzyme System
  • Polychlorinated Biphenyls
  • Oxidoreductases
  • Glucose Oxidase
  • Cytochrome P-450 CYP1A1
  • Deferoxamine
  • 3,4,3',4'-tetrachlorobiphenyl
Topics
  • Aminolevulinic Acid (pharmacology)
  • Animals
  • Benzoflavones (pharmacology)
  • Cells, Cultured
  • Chick Embryo
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System (biosynthesis)
  • Deferoxamine (pharmacology)
  • Enzyme Induction (drug effects)
  • Glucose Oxidase (metabolism)
  • Male
  • Microsomes, Liver (drug effects, enzymology, metabolism)
  • Oxidation-Reduction
  • Oxidoreductases (biosynthesis)
  • Polychlorinated Biphenyls (pharmacology)
  • Porphyrias (chemically induced)
  • Porphyrinogens (metabolism)
  • Porphyrins (metabolism)
  • Rats
  • Rats, Inbred Strains
  • Species Specificity
  • Uroporphyrinogens (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: