title: Cyclophosphamide induces mRNA, protein and enzyme activity of cytochrome P450 in rat.
abstract: The effects of cyclophosphamide (CPA) on CYP enzymes in vivo and its auto induction in rat were investigated in Wistar/Fu male rats at a single dose (40 or 200 mg kg(-1)) or as repeated dose of 200 mg kg(-1) CPA. After a single dose of CPA, mRNAs of CYPs 2B1, 2B2, 3A2, 2C11 were significantly induced up to 220-, 6.7-, 5.0- and 5.8-fold at the low dose CPA, and 4800-, 52-, 22- and 2.5-fold at the high dose. CYP2B1/2 and CYP3A proteins were increased by 4- and 2-fold (low dose) and by 28- and 1.7-fold (high dose). CYP2C11 protein levels were not altered. Microsomal activities of CYP2B, CYP3A and 2C11 were increased by 2-, 1.8- and 1.3-fold at low dose CPA, and 3.2-, 1.7- and 1.6-fold at high dose. A significant (p<0.05) decrease in CPA concentration and a significant (p<0.05) increase in 4-OH-CPA levels were observed with repeated administration of CPA. Acute induction effect on CYP2B1, 2B2, 2C11 and 3A2 and a substantial up regulation of CYP2B1 mRNA were observed after a single dose of CPA, auto induction was observed by repeated administration.
authors: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden.
authors: H
authors: H
authors: Xie
authors: P
authors: P
authors: Afsharian
authors: Y
authors: Y
authors: Terelius
authors: R A
authors: RA
authors: Mirghani
authors: U
authors: U
authors: Yasar
authors: A-L
authors: AL
authors: Hagbjörk
authors: S
authors: S
authors: Lundgren
authors: Y
authors: Y
authors: Hu
authors: A
authors: A
authors: Rane
authors: M
authors: M
authors: Hassan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF
chemical_list: D012333:RNA, Messenger; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System