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 induction of hepatic microsomal cytochrome P450 (P450) and heme oxygenase was compared, and their effects on five different P450 isoforms (P4501A1, 3A2, 2B1, 2E1 and 2C11) in rat were examined. 2. Treatment of rat with 2,2'-dipyridyL amine resulted in the marked induction of haem oxygenase to about seven-fold of the controls with a decrease in p450 content. 2,2'-Dipyridyl ketone produced concomitant induction of both P450 and haem oxygenase activity in a dose- and time-dependent manner without showing any sex differences. 3. Immunoblot analysis revealed that 2,2'-dipyridyl ketone slightly increased CYP2E1 and CYP3A2 at low doses, but not at high dose levels. There was no effect on P4502C11. P4502B1 was induced by the treatment with 2,2'-dipyridyl 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 microsomal P450s and haem oxygenase.
Kobayashi
Y
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Ohshiro
N
N
Okui
E
E
Sasaki
T
T
Tokuyama
S
S
Yoshida
T
T
Yamamoto
T
T
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
C418768:2,2'-dipyridylketone; D007527:Isoenzymes; D015082:2,2'-Dipyridyl; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); C048062:2,2'-dipyridylamine