Concurrent induction of rat hepatic microsomal cytochrome P450 and haem oxygenase by 2,2 '-dipyridyl ketone: comparison with the effect of 2,2 '-dipyridyl amine

1. The effect of 2,2'-dipyridyl ketone and 2,2'-dipyridyl amine on the indu ction of hepatic microsomal cytochrome P450 (P450) and heme oxygenase was c ompared, and their effects on five different P450 isoforms (P4501A1, 3A2, 2 B1, 2E1 and 2C11) in rat were examined. 2. Treatment of rat with 2,2'-dipyridyl amine resulted in the marked induct ion of haem oxygenase to about seven-fold of the controls with a decrease i n P450 content. 2,2'-Dipyridyl ketone produced concomitant induction of bot h P450 and haem oxygenase activity in a dose- and time-dependent manner wit hout showing any sex differences. 3. Immunoblot analysis revealed that 2,2'-dipyridyl ketone slightly increas ed CYP2E1 and CYP3A2 at low doses, but not at high dose levels. There was n o effect on P4502C11. P4502B1 was induced by the treatment with 2,2'-dipyri dyl ketone in a dose-dependent manner. 4. These results indicate that dipyridyl compounds having different bridges between two aromatic moieties act as differential inducers of hepatic micr osomal P450s and haem oxygenase.