Cyclophosphamide induces mRNA, protein and enzyme activity of cytochrome P450 in rat

Xenobiotica. 2005 Mar;35(3):239-51. doi: 10.1080/00498250500057369.

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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclophosphamide / pharmacology*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Male
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology*
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred WF

Substances

  • RNA, Messenger
  • Cyclophosphamide
  • Cytochrome P-450 Enzyme System