EFFECT OF PYRIDINE AND PYRIDINE-N-OXIDE ON THE MONOOXYGENASE SYSTEM OF RAT-LIVER MICROSOMES

Effects of administrations of pyridine and pyridine-N-oxide to rats on the monooxygenase system of liver microsomes were investigated. Admin istration of pyridine at a dose of 200 mg/kg resulted, after 24 h, in increase in total content of cytochrome P-450 and enhancement of metab olism of certain substrates in liver microsomes. Thus, enhanced activi ty was observed for hydroxylation of p-nitrophenol (PNP) and chlorzox azone (CZ) which was caused by increase in the microsomal level of an ethanol-inducible form of cytochrome p-450IIE1. Pyridine could also in duce microsomal cytochrome P-450IIB1 which was accompanied with increa se in the O-dealkylation rate of 7-pentoxyresorufin (PR). In addition, the appearance of cytochrome P-450IA1 and increase in content of cyto chrome P-450IA2 were observed in rat liver microsomes, as well as high er dealkylation rates of 7-ethoxyresorufin (ER) and 7-methoxyresorufin (MR) which are specific substrates for these cytochrome forms. Pyridi ne-N-oxide, like pyridine, induced cytochromes P-450IIE1, IIB1/B2, and IA1/A2 in rat liver and this was accompanied by enhanced metabolism o f the specific substrates. Thus, pyridine and its derivative pyridine- N-oxide are effective inducers of cytochrome P-450.