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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F04%3A00000855%21RIV%2F2005%2FGA0%2F151105%2FN
rdf:type
skos:Concept n19:Vysledek
dcterms:description
Sanguinarin (SA) je benzo[c]fenanthridinový alkaloid s antimikrobiálními, protizánětlivými a protirakovinovými vlastnostmi. Jeho použití v medicíně je však omezeno jeho toxicitou. Podle Williamse et al. [Vet. Hum. Toxicol. 42 (2000) 196] má potkaní jaterní cytochrom P450 (CYP) 1A2 pravděpodobně schopnost ovlivňovat toxicitu SA. Po indukci CYP1A 2,3,7,8-tetrachlorodibenzo-p-dioxinem, 3-methylcholanthrenem a ß-naftoflavonem došlo opravdu v primární kultuře potkaních hepatocytů a v buňkách HepG2 ke snížení in vitro toxicity SA hodnocené stanovením aktivity laktátdehydrogenasy uvolněné do média a stanovením životnosti buněk MTT testem. Při použití mikrosomů obsahujících rekombinantní enzymy SA inhibuje nekompetitivně aktivitu CYP1A1 a kompetitivně aktivitu CYP1A2 sledovanou jako deethylaci 7-ethoxyresorufinu (EROD). U lidských jaterních mikrosomů SA inhibuje kompetitivně EROD aktivitu s hodnotou Ki 2 #M, která je shodná jako u rekombinantního CYP1A2. SA inhibuje také aktivitu NADPH:CYP-reduktasy, enzymu n 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 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
dcterms:title
Involvement of cytochrome P450 1A in sanguinarine detoxication Involvement of cytochrome P450 1A in sanguinarine detoxication Zapojení cytochromu P450 1A do detoxikace sanguinarinu
skos:prefLabel
Zapojení cytochromu P450 1A do detoxikace sanguinarinu Involvement of cytochrome P450 1A in sanguinarine detoxication Involvement of cytochrome P450 1A in sanguinarine detoxication
skos:notation
RIV/61989592:15110/04:00000855!RIV/2005/GA0/151105/N
n3:strany
375-387
n3:aktivita
n4:Z n4:P
n3:aktivity
P(GP303/01/P085), Z(MSM 151100003)
n3:cisloPeriodika
2
n3:dodaniDat
n12:2005
n3:domaciTvurceVysledku
n11:8341362 n11:1030957 n11:1810596 n11:2514559
n3:druhVysledku
n17:J
n3:duvernostUdaju
n6:S
n3:entitaPredkladatele
n9:predkladatel
n3:idSjednocenehoVysledku
568951
n3:idVysledku
RIV/61989592:15110/04:00000855
n3:jazykVysledku
n16:eng
n3:klicovaSlova
Sanguinarine;cytochrome P450;toxicity;human hepatic microsomes;NADPH : CYP reductase
n3:klicoveSlovo
n7:toxicity n7:cytochrome%20P450 n7:Sanguinarine n7:NADPH%20%3A%20CYP%20reductase n7:human%20hepatic%20microsomes
n3:kodStatuVydavatele
IE - Irsko
n3:kontrolniKodProRIV
[5EFD076A24AC]
n3:nazevZdroje
Toxicology Letters
n3:obor
n5:CE
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
4
n3:projekt
n15:GP303%2F01%2FP085
n3:rokUplatneniVysledku
n12:2004
n3:svazekPeriodika
151
n3:tvurceVysledku
Modrianský, Martin Kosina, Pavel Vrba, Jiří Ulrichová, Jitka
n3:zamer
n14:MSM%20151100003
s:issn
0378-4274
s:numberOfPages
13
n18:organizacniJednotka
15110