Microsomal cytochrome P-450 "handprints": five fractions from anion-exchange high-pressure liquid chromatography provide a rapid preliminary screen for selectivity in the induction and destruction of rat hepatic cytochrome P-450 subpopulations.
Anion-exchange HPLC was used to monitor changes in rat hepatic cytochrome P-450 fractions resulting from animal exposure to several inducing and hepatotoxic agents. The column eluant was divided into five fractions and the cytochrome P-450 content in each was determined. Induction of hepatic cytochrome P-450 following 2,5-hexanedione and SKF 525-A pretreatment of animals showed an induction pattern in the five-fraction "handprint" similar to that produced by phenobarbital. The patterns of induction following beta-naphthoflavone, clofibrate, and isosafrole pretreatments were unique in comparison to each other and also compared to that of phenobarbital. The pattern of cytochrome P-450 loss after allyl alcohol was similar to that seen after cobalt chloride treatment, but differed from that seen following acetaminophen administration. Five-fraction quantitation of the eluant from anion-exchange HPLC of microsomes appears to be a useful technique to screen for and convey the effects of previously uncharacterized inducers and the effects of hepatotoxic agents or heme synthesis inhibitors on rat hepatic cytochrome P-450 subpopulations.
D000818:Animals; D005591:Chemical Fractionation / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000145:classification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D003577:Cytochrome P-450 Enzyme System