title: In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2-(phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver microsomes.
abstract: Interference of antiviral agent adefovir, i.e. 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with microsomal drug metabolizing system was investigated in rats. The content of total liver cytochrome P450 (CYP) was lowered while that of its denaturated form, P420, was elevated in animals intraperitoneally treated with PMEA (25 mg/kg). Similar effect was observed after treatment with a prodrug of adevofir, adefovir dipivoxil (bisPOM-PMEA). The CYP2E1-dependent formation of 4-nitrocatechol from p-nitrophenol was diminished, though the specific activity of p-nitrophenol hydroxylase remained unchanged. PMEA had no influence on expression of CYP2E1 protein and mRNA and mRNAs of other P450 isoenzymes (1A1, 1A2, 2C11, 3A1, 3A2, and 4A1). It may be concluded that repeated systemic administration of higher doses of PMEA results in a partial degradation of rat CYP protein to inactive P420.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague. zidekz@biomed.cas.cz
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Zídek
authors.forename: Pavel
authors.initials: P
authors.lastname: Anzenbacher
authors.forename: Eva
authors.initials: E
authors.lastname: Anzenbacherová
authors.forename: Evzen
authors.initials: E
authors.lastname: Buchar
authors.forename: Eva
authors.initials: E
authors.lastname: Kmonícková
authors.forename: Petr
authors.initials: P
authors.lastname: Potmesil
authors.forename: Antonín
authors.initials: A
authors.lastname: Holý
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects*; D009596:Nitrophenols / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000998:Antiviral Agents; D002396:Catechols; D009596:Nitrophenols; D063065:Organophosphonates; D012333:RNA, Messenger; C053001:adefovir; D003577:Cytochrome P-450 Enzyme System; D000225:Adenine; C001833:4-nitrocatechol; C024836:4-nitrophenol