Induction of liver cytochrome P-450 in mice by warfarin. Comparison of warfarin-, phenobarbitone-, and cobalt-induced hepatic microsomal protein patterns by PAGE after partial purification on octyl-sepharose CL-4B.
A rapid method is presented to separate mouse liver cytochrome P-450 from other components of the microsomal monooxygenase system and to increase specific activity by hydrophobic interaction chromatography on Octyl-Sepharose CL-4B by a factor of between 3.8 and 5.3. In addition it is shown that varieties of cytochrome P-450 can be separated from each other by Octyl-Sepharose CL-4B. After oral applications of 120 mg/kg warfarin once daily for three days SDS-PAGE analysis of the partially purified cytochrome P-450 fraction revealed a protein pattern in the 50 Kd region that is practically indistinguishable from that after conventional phenobarbitone pretreatment. On the other hand, cobalt pretreatment results in a different pattern that is distinguished from that of normals as well as from that of phenobarbitone- and warfarin-pretreated mice. From these results in conjunction with the previous finding of increased drug metabolic activity after warfarin pretreatment it is concluded that warfarin elicits phenobarbitone-like induction of the hepatic monooxygenases in mice.
D000818:Animals; D002847:Chromatography, Agarose; D003035:Cobalt / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003580:Cytochromes / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000032:analysis* / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D011506:Proteins / Q000032:analysis*; D014859:Warfarin / Q000494:pharmacology*
D003580:Cytochromes; D011506:Proteins; D003035:Cobalt; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital