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

2000-11-01
Arinc, E
Adalı, Orhan
Gencler-Ozkan, AM
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.

Citation Formats
E. Arinc, O. Adalı, and A. Gencler-Ozkan, “Stimulation of aniline, p-nitrophenol and N-nitrosodimethylamine metabolism in kidney by pyridine pretreatment of rabbits,” ARCHIVES OF TOXICOLOGY, vol. 74, no. 9, pp. 527–532, 2000, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41474.