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Characterization of Hepatic Drug-metabolizing Activities of Bama Miniature Pigs (Sus scrofa domestica): Comparison with Human Enzyme Analogs

机译:巴马小型猪(家蝇)的肝脏药物代谢活性的表征:与人类酶类似物的比较

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WeusedvarioussubstratesandselectiveinhibitorsofhumancytochromeP450(CYP)isozymesasprobestostudythemetabolismoflivermicrosomesfromChineseBamaminiaturepigs.Nifedipineoxidation(NOD)andtestosterone6#59137;-hydroxylation(6#59137;-OHT)activitiesweresimilarbetweenhumanlivermicrosomesandthosefromBamaminiaturepigs.However,comparedwiththosefromhumans,livermicrosomesfromBamaminiaturepigsshoweddecreasedphenacetinO-deethylation,coumarin7-hydroxylation,andchlorzoxazone6-hydroxylationactivities,whereasdextromethorphanO-demethylationactivitywasincreased.KetoconazoleselectivelyinhibitedNODand6#59137;-OHTactivitiesinmicrosomesfromBamapigs,and8-methoxypsoralenandtranylcypromineinhibitedcoumarin7-hydroxylationinpigmicrosomes.However,furafyllineandquinidinefailedtoselectivelyinhibitphenacetinO-deethylationanddextromethorphanO-demethylationinmicrosomesfromBamapigs,whereaschlormethiazolemoreefficientlyinhibitedcoumarin7-hydroxylationactivitythanchlorzoxazone6-hydroxylationinpigmicrosomes.OurresultssuggestthatlivermicrosomesfromChineseBamaminiaturepigsaresimilartothosefromhumansinregardtometabolismofnifedipineandtestosterone(bothareprobesubstratesforhumanCYP3A4).Inaddition,chemicalinhibitorsusedasspecificprobesforhumanP450enzymesdidnotalwaysshowthesameselectivitytowardcorrespondingenzymeactivitiesinlivermicrosomesfromBamapigs.However,ketoconazole(apotentinhibitorofhumanCYP3A4)couldbeusedasaselectiveinhibitorprobefortheNODand6#59137;-OHTactivitiesinlivermicrosomesfromChineseBamaminiaturepigs.
机译:WeusedvarioussubstratesandselectiveinhibitorsofhumancytochromeP450(CYP)isozymesasprobestostudythemetabolismoflivermicrosomesfromChineseBamaminiaturepigs.Nifedipineoxidation(NOD)andtestosterone6#59137;羟基化(6#59137; -OHT)activitiesweresimilarbetweenhumanlivermicrosomesandthosefromBamaminiaturepigs.However,comparedwiththosefromhumans,livermicrosomesfromBamaminiaturepigsshoweddecreasedphenacetinO-脱乙基化,coumarin7羟化,andchlorzoxazone6-hydroxylationactivities,whereasdextromethorphanO-demethylationactivitywasincreased.KetoconazoleselectivelyinhibitedNODand6#59137; Bamapigs的微粒体中的-OHT活性和8-甲氧基补骨脂素和反式环丙胺抑制了猪微粒体中的香豆素7-羟基化。但是,呋喃茶碱和奎尼丁未能选择性地抑制Bamapigs的六甲基苯甲酰邻苯二酚O-去乙基羟基和右甲基甲氧基O-去甲基化羟基,因此我们认为,氯霉素对苯甲酰氯的影响很小。 livermicrosomesfromChineseBamaminiaturepigsaresimilartothosefromhumansinregardtometabolismofnifedipineandtestosterone(bothareprobesubstratesforhumanCYP3A4).Inaddition,chemicalinhibitorsusedasspecificprobesforhumanP450enzymesdidnotalwaysshowthesameselectivitytowardcorrespondingenzymeactivitiesinlivermicrosomesfromBamapigs.However,酮康唑(apotentinhibitorofhumanCYP3A4)couldbeusedasaselectiveinhibitorprobefortheNODand6#59137; -OHTactivitiesinlivermicrosomesfromChineseBamaminiaturepigs。

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