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Titolo:
CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers
Autore:
Donato, MT; Viitala, P; Rodriguez-Antona, C; Lindfors, A; Castell, JV; Raunio, H; Gomez-Lechon, MJ; Pelkonen, O;
Indirizzi:
Hosp Univ La Fe, Ctr Invest, Unidad Hepatol Expt, E-46009 Valencia, Spain Hosp Univ La Fe Valencia Spain E-46009 tol Expt, E-46009 Valencia, Spain Univ Oulu, Dept Pharmacol & Toxicol, Oulu, Finland Univ Oulu Oulu Finland iv Oulu, Dept Pharmacol & Toxicol, Oulu, Finland
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 11, volume: 28, anno: 2000,
pagine: 1321 - 1326
SICI:
0090-9556(200011)28:11<1321:CEIMAH>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
COUMARIN 7-HYDROXYLATION; CYTOCHROME-P450 ISOZYMES; PORPHYRINOGENIC AGENTS; LIVER-MICROSOMES; PRIMARY CULTURE; MESSENGER-RNA; INDUCTION; PYRAZOLE; MICE; PURIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Gomez-Lechon, MJ Hosp Univ La Fe, Ctr Invest, Unidad Hepatol Expt, Avda Campanar 21, E-46009 Valencia, Spain Hosp Univ La Fe Avda Campanar 21 Valencia Spain E-46009
Citazione:
M.T. Donato et al., "CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers", DRUG META D, 28(11), 2000, pp. 1321-1326

Abstract

Induction of coumarin 7-hydroxylation, catalyzed by CYP2A5 in mice and CYP2A6 in humans by various known in vivo murine inducers and modifiers, was compared in human and mouse hepatocytes in culture. Phenobarbital and rifampicin were efficient inducers (up to 10-fold induction) after 48-h treatmentin murine cultured hepatocytes, whereas the enzyme activity in human hepatocytes was much more refractory to induction. However, a prolongation of incubation time to 72 h in human hepatocytes led to a modest restoration of inducibility by phenobarbital. Of the three porphyrinogenic inducers studied, griseofulvin induced the murine enzyme efficiently, but not the human enzyme, whereas aminotriazole and thioacetamide had no effect on either species. Pyrazole produced substantial induction in both human and murine hepatocytes, whereas cobalt chloride, which is also an in vivo inducer of the mouse enzyme, had no effect. Clofibric acid, an in vivo depressor of coumarin 7-hydroxylase, also depressed hepatocyte activities. In both murine and human hepatocytes, changes in CYP2A5/6 mRNA levels correlated roughly with enzyme changes, except in the case of cobalt chloride, which increased mRNA levels despite a lack of effect on enzyme activity. In general, human and mouse hepatocytes gave a similar response to CYP2A inducers. However, some differences were found, which means that, although CYP2A isozymes are probably regulated in a similar manner in both species, it is necessary to be cautious before extrapolating to human the results found in mouse models.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 12:33:19