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1.
Cytochrome P450 monoxygenase converts arachionic acid to four epoxyeicosatrienoic acid regiosomes: 5, 6-EET (epoxyeicosatrienoic acid); 8, 9-EET; 11, 12-EET and 14, 15-EET. Recent studies show that EETs are involved in signal transduction. EETs open Ca2+-sensit ive K+ channel and inhibit Na+ channel, Ca2+-sensitive Cl- channel and so on. What is more, EETs have been demonstrated to activate PP60c-src and initiate a tyrosine kinase cascade that mediates mitogenic effects.  相似文献   
2.
The acute toxicities of two organophosphorodithioate (dimethoate and disulfoton) and two organophosphorothioate (omethoate and demeton-S-methyl) insecticides were evaluated individually and in binary combination with the herbicide atrazine using fourth-instar larvae of the aquatic midge, Chironomus tentans. Atrazine alone up to 1000 μg/L did not show significant toxicity to the midges in a 48-h bioassay. However, atrazine concentrations as low as 1 μg/L in combination with dimethoate at EC25 (concentration to affect 25% of tested midges), 100 μg/L in combination with disulfoton (EC25), and 10 μg/L in combination with demeton-S-methyl (EC25) significantly enhanced the toxicity of each organophosphate insecticide. In contrast, atrazine concentrations of 10 μg/L and above in combination with omethoate (EC25) significantly decreased the toxicity of the insecticide. Biochemical analysis indicated that increased toxicity of dimethoate, disulfoton, and demeton-S-methyl in binary combination with atrazine correlated to the increased inhibition of acetylcholinesterase. Furthermore, cytochrome P450-dependent O-deethylation activity in the midges exposed to atrazine at 1000 μg/L was 1.5-fold higher than that in the control midges. Thus, atrazine appeared to induce cytochrome P450 monooxygenases in the midges. Elevated cytochrome P450 monooxygenase activity may increase the toxicities of dimethoate, disulfoton, and demeton-S-methyl by enhancing the oxidative activation of dimethoate into omethoate, and disulfoton and demeton-S-methyl into their sulfoxide analogs with increased anticholinesterase activity. In contrast, atrazine reduced the toxicity of omethoate possibly by enhancing the oxidative metabolic detoxification since omethoate does not require oxidative activation.  相似文献   
3.
The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug–drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450‐mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma‐hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5‐OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5‐OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug–drug interactions and identification of reasons for varying pharmacokinetics between horses.  相似文献   
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昆虫体内的细胞色素P450酶系统在昆虫解毒过程中发挥着重要作用。本次试验通过转录组测序获得一条新的黏虫P450基因,经国际委员会命名为CYP9A134(登录号为MT990973)。该序列全长为1801 bp,开放序列长度为1596 bp,编码531个氨基酸,分子质量为61.42 kDa,等电点为4.90。在黏虫幼虫阶段用2.5%高效氯氟氰菊酯和20%氯虫苯甲酰胺诱导时该基因表达量会有不同程度上升,最高的可分别达对照组的2.6倍和6.5倍。RNA干扰后,该基因表达量最低下降了70%,以上2种杀虫剂LD30杀虫效果分别提高了13%和25%;在黏虫成虫阶段用20%氯虫苯甲酰胺LD30诱导时,该基因表达量最高可达7.8倍。RNA干扰后,该基因表达量最低下降了61%,LD30剂量的氯虫苯甲酰胺杀虫效果提高26%。结果表明,该基因可能在杀虫剂诱导的解毒代谢过程中发挥重要作用。  相似文献   
6.
Phenolic compounds and carotenoids are potential inhibitors of cytochrome P450s. Sixteen known compounds, phenolic compounds and carotenoids from seaweed were examined for potential inhibitory capacity against CYP1A2 and CYP3A4 in silico and in vitro. Morin, quercetin, and fucoxanthin inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose-dependent manner. The IC50 values of morin, quercetin, and fucoxanthin were 41.8, 22.5, and 30.3 μM for CYP1A2 and 86.6, 16.1, and 24.4 μM for CYP3A4, respectively. Siphonaxanthin and hesperidin did not show any significant effect on CYP1A2, but they slightly inhibited CYP3A4 activity at high concentrations. In silico modeling of CYP’s binding site revealed that the potential inhibitors bound in the cavity located above the distal surface of the heme prosthetic group through the 2a or 2f channel of CYPs. This study presents an approach for quickly predicting CYP inhibitory activity and shows the potential interactions of compounds and CYPs through in silico modeling.  相似文献   
7.
为明确东北稻区稻稗Echinochloa oryzoides HJHL-715种群对五氟磺草胺的抗性水平及抗性机制,采用整株生物测定法测定稻稗种群对五氟磺草胺的敏感性,明确抗性种群的交互抗性和多抗性情况,研究3种细胞色素P450抑制剂对其敏感性的影响;并应用分子生物学方法进行稻稗的乙酰乳酸合酶(acetolactate synthase,ALS)离体活性测定、ALS基因序列分析及其表达量测定。结果表明:在东北稻区,五氟磺草胺对稻稗HJHL-715种群鲜重的抑制中剂量GR50为62.53 g/hm^2;稻稗HJHL-715的ALS基因序列中未发现氨基酸突变,其ALS离体活性与敏感种群的ALS离体活性无显著性差异,ALS基因表达量显著低于敏感种群。1-氨基苯并三唑(1-aminobenzotriazole,ABT)、胡椒基丁醚(piperomyl butoxide,PBO)、马拉硫磷3种P450抑制剂显著提高了稻稗HJHL-715种群对五氟磺草胺的敏感性,使其对五氟磺草胺的GR50由原来的62.53 g/hm^2分别下降到5.78、5.02、3.53 g/hm^2。表明东北稻区已经出现了对五氟磺草胺具有高水平抗性的稻稗种群,稻稗HJHL-715种群对五氟磺草胺的抗性很可能是由细胞色素P450介导的代谢增强所致。  相似文献   
8.
为筛选出黏虫Mythimna separata参与杀虫剂解毒代谢的主效细胞色素P450基因,采用叶片浸渍法测定了用于处理黏虫3龄幼虫的亚致死浓度,通过构建转录组测序文库并结合数字基因表达(digital gene expression,DGE)对不同处理的黏虫进行测序,并运用实时荧光定量PCR(realtime quantitative polymerase chain reaction,RT-qPCR)技术验证12个P450基因的表达情况。结果表明,用于处理黏虫的氯虫苯甲酰胺和氟虫腈亚致死浓度LC_(10)分别为0.15、13.66 mg/L;对照样品、氟虫腈处理样品和氯虫苯甲酰胺处理样品分别获得59 521 504、64 838 148和41 722 990个原始序列数据,分别获得57 441 216、62 368 912和40 285 164个过滤后的序列数据;过滤后的序列长度分别为8.62、9.36和6.04 G;碱基错误率均为0.02%;Phred数值大于20、30的碱基占总碱基的百分比均高于90.59%;鸟嘌呤+胞嘧啶(guanine cytosine,GC)含量分别为47.16%、48.94%和47.55%,表明转录组测序质量较高;黏虫受氯虫苯甲酰胺胁迫后,29个P450基因表达量上调,27个P450基因表达量下调;黏虫受氟虫腈胁迫后,23个P450基因表达量上调,26个P450基因表达量下调;12个P450基因表达量的RT-qPCR技术检测结果与DGE测序文库显示的结果基本一致。  相似文献   
9.
Cytochrome P450 (CYP) 1A1 participates in the activation as well as detoxification of environmental pollutants such as aromatic hydrocarbons. This CYP form is also efficiently induced by aromatic hydrocarbons. The presence of CYP 1A1 in the brain might thus be of physiological and toxicological importance. In the present investigation on rainbow trout, the distribution of 7-ethoxyresorufin-O-deethylase (EROD) activity, a cytochrome CYP 1A1 catalyzed reaction, was measured in whole tissue homogenates from brain parts. In control fish, a relatively high activity was found in the rainbow trout olfactory bulb compared to the other brain parts. Although an EROD induction (3 to 7-fold) by β-naphthoflavone (BNF) was recorded in all brain parts from the rainbow trout, the highest induced activity was measured in the olfactory bulbs. To ascertain the distribution of EROD activity in cells, whole brain tissue was subfractionated by differential centrifugation. The fractionation scheme separated mitochondria (P2 fraction) and microsomes (P3 fraction) as determined by marker enzymes and electron microscopy. In control rainbow trout, a low EROD activity could be measured in the P2 fraction. BNF induced the EROD activity in both P2 and P3 fractions. Western blotting showed the induction by BNF of a protein band in the P2 and P3 fractions with a molecular mass around 58,000 when highly specific anti-cod CYP 1A1 antibodies were used. ELISA measurements confirmed the induction of CYP 1A1 protein in the rainbow trout brain subcellular fractions.  相似文献   
10.
CYP酶代谢是药物生物转化的主要途径,其数量和活性大小直接影响药物在体内的活化与代谢。我们对草鱼肝微粒体CYP酶含量及其活性进行了初步研究,以差速离心法提取草鱼肝微粒体,以CO还原差示光谱法测得CYP酶及细胞色素b5含量分别为0.619±0.102 nmol/mg、0.264±0.042 nmol/mg。以7-乙氧异吩噁唑酮-O-脱乙基反应、苯胺-4-羟化反应、氨基比林-N-脱甲基反应作为CYP1A、CYP2E、CYP3A的探针反应,测得EROD酶活为0.043±0.004 nmol/mg/min,ANH酶活为0.028±0.002 nmol/mg/min,AMND酶活为0.207±0.035 nmol/mg/m in。结果表明草鱼肝微粒体中CYP酶发育完好,并且具有参与药物代谢的3种主要亚型活性,其含量与活性大小与其它实验动物相差较大。本实验的方法与结果为草鱼CYP酶的系统研究提供可靠手段,最终为指导水产合理用药提供理论依据。  相似文献   
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