Stimulation of aniline, p-nitrophenol and N-nitrosodimethylamine metabolism in kidney by pyridine pretreatment of rabbits

Arinc E., Adali O., Gencler-Ozkan A.

ARCHIVES OF TOXICOLOGY, vol.74, no.9, pp.527-532, 2000 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 74 Issue: 9
  • Publication Date: 2000
  • Doi Number: 10.1007/s002040000164
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.527-532
  • Keywords: pyridine, kidney, nitrosodimethylamine N-demethylase, p-nitrophenol hydroxylase, aniline 4-hydroxylase, ALCOHOL-INDUCIBLE FORM, RAT HEPATOCYTES, MICROSOMAL CYTOCHROME-P-450, PARA-AMINOPHENOL, CIGARETTE-SMOKE, INDUCTION, LIVER, EXPRESSION, LUNG, BENZENE
  • Middle East Technical University Affiliated: Yes


Pyridine has been shown to cause liver and kidney damage in animals and in humans. In a previous study we examined the effects of pyridine on rabbit liver and lung microsomal drug-metabolizing enzymes. In this study, in vivo i.p. administration of pyridine to rabbits caused a significant 3.4-fold increase in kidney N-nitrosodimethylamine (NDMA) N-demethylase activity as compared to the activity in control rabbits. The same treatment also significantly stimulated the activity of other cytochrome P4502E1-associated enzymes. The activities of p-nitrophenol hydroxylase and aniline 4-hydroxylase in kidney microsomes were increased 4.9- and 4.5-fold, respectively. Pyridine treatment increased the P450 content of the kidney 1.6-fold (P < 0.05). SDS-PAGE of both kidney and liver microsomes of pyridine-treated rabbits showed a protein band of enhanced intensity at 51,000 Mr migrating in the region of cytochrome P4502E1. p-Aminophenol, a 4-hydroxylation product of aniline, has been shown to be nephrotoxic and NDMA, a procarcinogen, has been shown to be carcinogenic following bioactivation by NDMA N-demethylase in a number of tissues including the kidney. Since pyridine was shown to be nephrotoxic, it is expected that pyridine potentiates the toxic and/or carcinogenic effects of aniline, p-nitrophenol and NDMA through induction of their metabolism by the cytochrome P450-dependent drug-metabolizing enzymes.