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

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