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首页> 外文期刊>Life sciences >Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases.
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Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases.

机译：甘草和甘草甜素对小鼠肝脏CYP依赖性单加氧酶的影响。

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This study is aimed to investigate the effect of the prolonged intake of conspicuous amounts of licorice (LE), or its natural constituent glycyrrhizin (G) on murine liver CYP-catalyzed drug metabolism. For this purpose the modulation of the regio- and stereo-selective hydroxylation of testosterone, together with the use of highly specific substrates as probes for different CYP isoforms such as ethoxyresorufin (CYP1A1), methoxyresorufin (1A2), pentoxyresorufin (2B1), p-nitrophenol (2E1) and aminopyrine (3A), were investigated. Daily doses of licorice root extract (3,138 or 6,276 mg/kg b.w. per os), or G (240 or 480 mg/kg b.w. per os), were administered to different groups of Swiss Albino CD1 mice of both sexes for 1, 4 or 10 consecutive days. While a single LE or G dose was unable to affect the multienzymatic CYP-system, using both schedules of repeated treatment, either LE or G were able to significantly induce hepatic CYP3A- and, to a lesser extent, 2B1- and 1A2-dependent microsomal monooxygenase activities, as well as 6beta- (mainly associated to CYP3A), 2alpha-, 6alpha- (CYP2A1, 2B1), 7alpha-, 16alpha- (CYP2B9) and 16beta-testosterone hydroxylase (TH) activities in male and female mice. Data on CYP3A modulation, the major isoform present in human liver, was confirmed by using Western immunoblotting with anti-CYP3A1/2 rabbit polyclonal antibodies raised against purified rat CYP3A. Northern blotting analysis using CYP3A cDNA biotinylated probe showed that the expression of such isozyme is regulated at the mRNA level. These results suggest that the induction of cytochrome P450-dependent activities by the prolonged intake of high LE or G doses, may result in accelerated metabolism of coadministered drugs with important implications for their disposition. The adverse effects associated with CYP changes such as toxicity/cotoxicity and comutagenicity may also have clinical consequences.
机译：这项研究的目的是调查延长摄入大量甘草（LE）或其天然成分甘草甜素（G）对小鼠肝脏CYP催化的药物代谢的影响。为此目的，调节睾丸激素的区域和立体选择性羟基化，并使用高度特异性的底物作为不同CYP亚型的探针，例如乙氧基间苯二酚（CYP1A1），甲氧基间苯二酚（1A2），戊氧基间苯二酚（2B1），对-研究了硝基苯酚（2E1）和氨基比林（3A）。对不同性别的瑞士白化CD1小鼠的每日一组分别给予每日剂量的甘草根提取物（3,138或6,276 mg / kg bw / os）或G（240或480 mg / kg bw / os）连续10天。虽然单剂量的LE或G不能影响多酶CYP系统，但使用这两种重复治疗方案，LE或G都能显着诱导肝脏CYP3A-依赖性，并在较小程度上诱导2B1和1A2依赖性微粒体单加氧酶活性以及雄性和雌性小鼠的6beta-（主要与CYP3A相关），2alpha-，6alpha-（CYP2A1、2B1），7alpha-，16alpha-（CYP2B9）和16beta-睾丸激素羟化酶（TH）活性。 CYP3A调节的数据是人肝脏中主要的同种型，通过使用针对纯化的大鼠CYP3A的抗CYP3A1 / 2兔多克隆抗体进行Western免疫印迹证实。使用CYP3A cDNA生物素化探针进行Northern印迹分析表明，这种同功酶的表达在mRNA水平受到调节。这些结果表明，延长摄入高剂量LE或G诱导的细胞色素P450依赖性活性可能导致共同给药药物的代谢加快，这对它们的处置具有重要意义。与CYP改变相关的不良反应，例如毒性/共毒性和致突变性，也可能产生临床后果。

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