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首页> 外文会议>International Conference on Energy, Environment and Sustainable Development >Inhibition of cytochrome P450 3A1/2 by organotin compound di-n-butyl-(4-chlorobenzohydroxamato)tin (IV) chloride in rat liver and BRL cells
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Inhibition of cytochrome P450 3A1/2 by organotin compound di-n-butyl-(4-chlorobenzohydroxamato)tin (IV) chloride in rat liver and BRL cells

机译：通过有机锡化合物二叔丁基 - （4-氯苯羟基）锡（IV）在大鼠肝脏和BRL细胞中抑制细胞色素P450 3A1 / 2的抑制

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Organotin compounds are high toxiferous chemicals and ubiquitous in our environment, which also have high biological activities. Di-n-butyl-(4-chlorobenzohydroxamato)tin (IV) chloride (DBDCT) represents a new paradigm for tin-based antitumor complexes with high activity. The inhibitory effect of DBDCT on cytochrome P450 3A(CYP3A) was studied in this article. The adult male SD rats were randomly divided into five groups with six in each and treated separately with saline, lipopolysaccharide (LPS, 5mg/kg), DBDCT (1.25, 2.5 and 5.0mg/kg, respectively) intraperitoneally for 2 days after induced with dexamethasone (DEX) at a dose of 100mg/kg for 4 days. The cytochrome P450 (CYP450) content was assayed by the method of Omura and Santa after the protein concentration detected by BCA assay kit. The activity of CYP3A was determined by the method of Nash. Western blot analysis was used to detect the expression of CYP3A1/2 at protein level in rat liver microsomes and Buffalo Rat Liver (BRL) cells. The results demonstrated that the activity of CYP450 and CYP3A were inhibited by exposure to DBDCT in rat liver compared with that of the blank control group. The expression of CYP3A1 and CYP3A2 proteins in rats treated with 1.25, 2.5 and 5.0mg/kg DBDCT were down-regulated respectively by 22.8% (p<0.01),24.3%(p<0.01), 58.4%(p<0.001) and 37.6%(p<0.001), 41.4%(p<0.001), 49.2%(p<0.001), than that of the blank control group. Immunoblot analysis of protein from BRL cell lysate demonstrated that the expression of CYP3A1 and CYP3A2 protein reduced separately by 11.4% (p<0.05), 34.2%(p<0.001), 45.5%(p<0.001), 64.9%(p<0.001), 78.8%(p<0.001) and 12.8% (p<0.05), 9.9% (p<0.05), 28.0% (p<0.001), 24.9% (p<0.001), 34.2% (p<0.001) after treated with DBDCT at a dose of 1μmol/L (for 24, 36, 48h) and 2μmol/L(for 24 and 48h). The activity of CYP3A in rat liver microsomes was decreased remarkably compared with that of the blank control group. Immunoblot analysis showed that the expression of CYP3A1/2 was inhibited significantly by DBDCT in rat liver and BRL cells.
机译：有机锡化合物是我们的环境中具有高毒性的化学品和普遍存在的环境，这也具有高生物活性。二 - 丁基 - （4-氯苯羟基）锡（IV）氯化锡（DBDCT）代表具有高活性的基于锡的抗肿瘤配合物的新范式。本文研究了DBDCT对细胞色素P450 3A（CYP3A）的抑制作用。将成年雄性SD大鼠随机分为五组，每次分为六个群，并分别用盐水，脂多糖（LPS，5mg / kg），DBDCT（分别为1.25,2.5和5.0mg / kg）诱导后2天内腹膜内腹膜内腹膜内腹膜内腹膜内腹膜内分别处理地塞米松（DEX）的剂量为100mg / kg 4天。通过BCA测定试剂盒检测到的蛋白质浓度后，通过核心和Santa的方法测定细胞色素P450（CYP450）含量。 CYP3A的活性由纳什方法确定。 Western印迹分析用于检测大鼠肝微粒体和水牛大鼠肝（BR1）细胞中蛋白质水平的CYP3A1 / 2的表达。结果表明，与坯料对照组相比，通过在大鼠肝脏中暴露于DBDCT来抑制CYP450和CYP3A的活性。用1.25,2.5和5.0mg / kg DBDCT处理的大鼠CYP3A1和CYP3A2蛋白的表达分别下调22.8％（P <0.01），24.3％（P <0.01），58.4％（P <0.001）和37.6％（P <0.001），41.4％（P <0.001），49.2％（P <0.001），而不是空白对照组。来自BRL细胞裂解物的蛋白质的免疫斑分析证明CYP3A1和CYP3A2蛋白的表达分别减少11.4％（P <0.05），34.2％（P <0.001），45.5％（P <0.001），64.9％（P <0.001 ），78.8％（P <0.001）和12.8％（P <0.05），9.9％（P <0.05），28.0％（P <0.001），24.9％（P <0.001），34.2％（P <0.001）之后用1μmol/ L（24,36,48h）和2μmol/ L（24和48h）的剂量处理DBDCT处理。与空白对照组相比，大鼠肝微粒体中CYP3A的活性显着降低。免疫斑分析表明，CYP3A1 / 2的表达被DBDCT在大鼠肝脏和BRL细胞中显着抑制。

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