"[5EFD076A24AC]" . . . "Modriansk\u00FD, Martin" . "4"^^ . . . "0378-4274" . . "RIV/61989592:15110/04:00000855!RIV/2005/GA0/151105/N" . . . "Involvement of cytochrome P450 1A in sanguinarine detoxication"@en . "Involvement of cytochrome P450 1A in sanguinarine detoxication" . . . . "2" . "4"^^ . . "RIV/61989592:15110/04:00000855" . . "IE - Irsko" . "Sanguinarine;cytochrome P450;toxicity;human hepatic microsomes;NADPH : CYP reductase"@en . "Sanguinarin (SA) je benzo[c]fenanthridinov\u00FD alkaloid s antimikrobi\u00E1ln\u00EDmi, protiz\u00E1n\u011Btliv\u00FDmi a protirakovinov\u00FDmi vlastnostmi. Jeho pou\u017Eit\u00ED v medic\u00EDn\u011B je v\u0161ak omezeno jeho toxicitou. Podle Williamse et al. [Vet. Hum. Toxicol. 42 (2000) 196] m\u00E1 potkan\u00ED jatern\u00ED cytochrom P450 (CYP) 1A2 pravd\u011Bpodobn\u011B schopnost ovliv\u0148ovat toxicitu SA. Po indukci CYP1A 2,3,7,8-tetrachlorodibenzo-p-dioxinem, 3-methylcholanthrenem a \u00DF-naftoflavonem do\u0161lo opravdu v prim\u00E1rn\u00ED kultu\u0159e potkan\u00EDch hepatocyt\u016F a v bu\u0148k\u00E1ch HepG2 ke sn\u00ED\u017Een\u00ED in vitro toxicity SA hodnocen\u00E9 stanoven\u00EDm aktivity lakt\u00E1tdehydrogenasy uvoln\u011Bn\u00E9 do m\u00E9dia a stanoven\u00EDm \u017Eivotnosti bun\u011Bk MTT testem. P\u0159i pou\u017Eit\u00ED mikrosom\u016F obsahuj\u00EDc\u00EDch rekombinantn\u00ED enzymy SA inhibuje nekompetitivn\u011B aktivitu CYP1A1 a kompetitivn\u011B aktivitu CYP1A2 sledovanou jako deethylaci 7-ethoxyresorufinu (EROD). U lidsk\u00FDch jatern\u00EDch mikrosom\u016F SA inhibuje kompetitivn\u011B EROD aktivitu s hodnotou Ki 2 #M, kter\u00E1 je shodn\u00E1 jako u rekombinantn\u00EDho CYP1A2. SA inhibuje tak\u00E9 aktivitu NADPH:CYP-reduktasy, enzymu n"@cs . . "Zapojen\u00ED cytochromu P450 1A do detoxikace sanguinarinu"@cs . "Involvement of cytochrome P450 1A in sanguinarine detoxication" . "P(GP303/01/P085), Z(MSM 151100003)" . . "Kosina, Pavel" . . . "13"^^ . "Sanguinarine (SA), a member of the benzo[c]phenanthridine alkaloids, is a potent anti-microbial agent with anti-inflammatory and anti-neoplastic properties. However, toxicity of the alkaloid severely limits its medical applications. Recent report by Williams et al. implicated rat hepatic cytochrome P450 (CYP) 1A2 as a likely modulator of SA toxicity. Indeed, the in vitro toxicity of SA in primary culture of rat hepatocytes and human hepatic cell line HepG2, demonstrated as lactate dehydrogenase leakage and metabolic capability (MTT assay), was diminished following induction of CYP1A by 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and beta-naphtoflavone. Using microsomes containing recombinant CYP1A1 or CYP1A2 we show that SA causes non-competitive inhibition of the former and competitive inhibition of the latter as assessed by ethoxyresorufin de-ethylation (EROD). In human hepatic microsomes SA exhibits competitive inhibition of EROD activity with apparent K(i) of 2 microM, a value ident"@en . "Sanguinarine (SA), a member of the benzo[c]phenanthridine alkaloids, is a potent anti-microbial agent with anti-inflammatory and anti-neoplastic properties. However, toxicity of the alkaloid severely limits its medical applications. Recent report by Williams et al. implicated rat hepatic cytochrome P450 (CYP) 1A2 as a likely modulator of SA toxicity. Indeed, the in vitro toxicity of SA in primary culture of rat hepatocytes and human hepatic cell line HepG2, demonstrated as lactate dehydrogenase leakage and metabolic capability (MTT assay), was diminished following induction of CYP1A by 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and beta-naphtoflavone. Using microsomes containing recombinant CYP1A1 or CYP1A2 we show that SA causes non-competitive inhibition of the former and competitive inhibition of the latter as assessed by ethoxyresorufin de-ethylation (EROD). In human hepatic microsomes SA exhibits competitive inhibition of EROD activity with apparent K(i) of 2 microM, a value ident" . . "Vrba, Ji\u0159\u00ED" . . . . "Zapojen\u00ED cytochromu P450 1A do detoxikace sanguinarinu"@cs . "Toxicology Letters" . "Ulrichov\u00E1, Jitka" . "568951" . "Involvement of cytochrome P450 1A in sanguinarine detoxication"@en . "15110" . . "151" . . "375-387" .