甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶系的影响

目的研究甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶系的影响。方法将Wistar大鼠分为空白对照组、甲磺酸加替沙星高、中、低剂量组（240、160、80mg·kg^-1）,ip,qd,共7d。采用差速离心法制备大鼠肝微粒体;BAC法测定蛋白浓度;分光光度法检测肝微粒体细胞色素P450酶含量及活性;单因素方差分析进行统计。结果给药组大鼠的肝重、微粒体细胞色素P450含量均明显降低,细胞色素b5的含量增高,但增高的趋势随剂量增加有所抑制;对NADPH-Cytc还原酶的影响：低、中剂量组与对照组比较有显著性差异（P〈0.01）,高剂量组与对照组比较无显著性差异（P〉0.05）,组间比较有显著性差异（P〈0.05）;对氨基比林-N-脱甲基酶和红霉素-N-脱甲基酶的影响：给药组与对照组比较有显著性差异（P〈0.01）,组间比较也有显著性差异（P〈0.05,P〈0.01）。另外,在中、高剂量组大鼠出现肝硬度增加、腹水等现象。结论甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶具有一定的影响,对NADPH-Cytc还原酶有诱导作用,对氨基吡啉-N-脱甲基酶和红霉素-N-脱甲基酶有抑制作用。可能引起肝药酶对某些药物代谢的改变。     

左旋氧氟沙星对大鼠肝重、肝微粒体蛋白质及细胞色素P450的影响

目的　研究和比较不同剂量左旋氧氟沙星对大鼠肝重、肝微粒体蛋白质及细胞色素P4 5 0含量的影响。方法　将大鼠分成空白对照组和给药组。采用连续给予不同剂量左旋氧氟沙星后 ,测定大鼠的肝重、肝微粒体蛋白质及细胞色素P4 5 0含量。给药方案为每组 80mg/kg、16 0mg/kg、2 4 0mg/kg ,腹腔注射给药1/d ,连续给药 7d。结果　给予不同剂量的左旋氧氟沙星后 ,大鼠的肝重及细胞色素P4 5 0含量均明显降低 ,中剂量组及高剂量组分别与对照组及低剂量组比较有极显著性差异 (P <0 0 1)。微粒体蛋白质含量各组间比较无差异 (P >0 0 5 )。结论　左旋氧氟沙星的这种作用可能引起肝药酶对某些药物代谢的改变。     

左旋氧氟沙星对大鼠肝重 肝微粒体蛋白质及细胞色素P450的影响

目的 研究和比较不同剂量给予左旋氧氟沙星后对大鼠肝重、肝微粒体蛋白质及细胞色素P450含量的影响.方法 将大鼠分成空白对照组和给药组.采用连续给予不同剂量左旋氧氟沙星后,测定大鼠的肝重、肝微粒体蛋白质及细胞色素P450含量.给药方案为每组80、160、240mg@kg-1,腹腔注射给药,qd,连续给药7d.结果 研究结果显示,给予不同剂量的左旋氧氟沙星后,大鼠的肝重及细胞色素P450含量均明显降低,中剂量组及高剂量组分别与对照组及低剂量组比较有极显著性差异(P<0.01).微粒体蛋白质含量各组间比较无差异(P>0.05).结论 左旋氧氟沙星的这种作用可能引起肝药酶对某些药物代谢的改变.     

1,5-二咖啡酰奎宁酸对大鼠肝微粒体细胞色素P450含量的影响

1,5-二咖啡酰奎宁酸(1,5-d icaffeoylqu in ic ac id,1,5-DC-QA)是我国近期自主研发的拟申报治疗艾滋病(acqu ired im-mune defic iency syndrom e,AIDS)的一类创新新药(药品注册管理办法,注册分类1),它为首次合成的全新化合物,其抑制人类免疫缺陷病毒(hum an immunodefic ienc     

1，5-二咖啡酰奎宁酸对大鼠所微粒体细胞色素P450含量的影响

1，5-二咖啡酰奎宁酸（1,5-dicaffeoylquini cacid，1，5-DCQA）是我国近期自主研发的拟申报治疗艾滋病（acquired immune deficiency syndrome，AIDS）的一类创新新药（药品注册管理办法，注册分类1），它为首次合成的全新化合物，其抑制人类免疫缺陷病毒（human immunodeficiency virus，HIV）的作用已经在细胞与整体动物等多种实验模型上得到证实。研究表明它的作用靶点为HIV-1整合酶，该酶是介导HIV基因组进入宿主染色体的一个关键性的酶。毒理学实验表明该药的毒性较低，提示该化合物为有独特作用特点的、毒副反应小的潜在新药。     

氟喹诺酮类药物在人肝微粒体对环孢霉素A代谢影响的研究

目的　研究 1 0种氟喹诺酮类药物对环孢霉素A代谢的影响。方法　采用人肝微粒体酶体外代谢试验 ,用荧光偏振免疫法测定环孢霉素A的浓度。结果　诺氟沙星、氧氟沙星、左氧沙星 ,司帕沙星、洛美沙星、培氟沙星和环丙沙星对环孢霉素A的代谢具有显著抑制作用 (P <0 .0 5 ) ;氟罗沙星、芦氟沙星和依诺沙星在相应浓度下未见对环孢霉素A的显著抑制。其抑制程度依次为 :洛美沙星 >氧氟沙星 >司帕沙星 >左氧沙星 >环丙沙星 >培氟沙星 >诺氟沙星 >氟罗沙星 >依诺沙星 >芦氟沙星。本体外试验数据与临床结果并不完全相关。结论　本试验结果提示某些氟喹诺酮药物对人细胞色素P450 中CsA代谢酶具有潜在的选择性抑制作用     

Ⅰ相药物代谢酶细胞色素P450及其与肝脏疾病的关系

细胞色素P450(CYP450)存在于多种组织和器官中,构成了一个血红素硫醇盐蛋白超家族,它在肝脏中的含量最为丰富,与肝脏疾病关系密切.CYP450是一个单氧化酶家族,对人类的Ⅰ相药物代谢具有重要意义,能够催化大量内源性和外源性复合物的代谢,包括异生物质、药物、环境毒物、类固醇和脂肪酸等.     

细胞色素P—450与电离辐射的关系

电离辐射可以改变细胞色素P-450(主要有CYP1Bl、CYPlAl、CYP4All、CYP2E1等)的活性和(或)mRNA、蛋白含量，从而影响药物代谢和有毒化学物的生物转化过程及其生物学作用。细胞色素P—450参与了生物还原活性物TMQ、AQ4N在机体内的还原。动物实验和已有的临床研究表明，调节P-450可以提高生物还原活性物的辐射增敏作用和抗肿瘤作用。     

复方丹参滴丸对大鼠肝CYP450酶系诱导作用的研究

目的观察复方丹参滴丸诱导处理对大鼠肝细胞色素P450及其主要亚型的影响.方法 Wistar大鼠用125、750、4 500mg*kg-1*d-1复方丹参滴丸连续灌胃诱导处理5d,测定微粒体中总CYP450含量和CYP1A2、2B1/2、2E1和3A亚型活性.结果不同剂量复方丹参滴丸诱导处理后大鼠肝脏脏器系数、总CYP450含量及CYP1A2、2E1、3A亚型活性未见明显增高.高剂量复方丹参滴丸诱导后,大鼠肝脏CYP2B1/2活性与空白对照组相比有显著升高(P<0.05),中、低剂量组CYP2B1/2活性未见明显升高.相应的阳性对照剂均导致肝脏CYP450及其亚型活性明显升高.结论复方丹参滴丸对大鼠肝脏CYP450及主要亚型CYP1A2、2E1、3A无诱导效应,高剂量下仅对CYP2B1/2有轻度诱导效应,此种作用无明显临床意义.     

中药对细胞色素P450诱导或抑制作用的影响因素

本文通过查阅近年来国内外有关中草药对CYP450影响的文献，并加以归纳、总结，综述了能够影响中药对CYP450诱导或抑制作用的各种药物因素和其他因素，从而指导和促进中草药对CYP450影响的研究。     

黄芩甙对小鼠肝细胞色素P450及其亚家族的诱导

目的：观察黄芩甙对小鼠肝细胞色素Ｐ４５０及其亚家族的影响,深入探讨黄芩甙保肝作用的机理。方法：采用分光光度法分别测定小鼠肝微粒体细胞色素Ｐ４５０、ｂ５含量及氨基比林Ｎ－脱甲基酶（ＡＤＭ）、７－乙氧基香豆素Ｏ－脱乙基酶（ＥＣＤ）、苯并芘羟化酶（ＡＨＨ）。采用蛋白印迹杂交技术鉴定细胞色素Ｐ４５０同功酶。结果：给小鼠黄芩甙（１００ｍｇ．ｋｇ＾－１．ｄ＾－１）灌胃,连续７ｄ,可使小鼠肝微粒体细胞色素Ｐ４５     

西咪替丁和水飞蓟宾对非酒精性脂肪性肝炎大鼠细胞色素P450的作用

目的:研究西咪替丁、水飞蓟宾对大鼠肝微粒体细胞色素P450(CYP450)表达的影响。方法:应用高脂饲料诱导的NASH大鼠模型,给予西咪替丁及水飞蓟宾灌胃,紫外分光光度计测量CYP450及同工酶CYP2E1含量,RT-PCR法检测TIMP-1、TIMP-2,生化分析仪测定转氨酶等指标。结果:与模型组比较,西咪替丁组大鼠的CYP450、CYP2E1、TIMP-1、TIMP-2含量均下降,ALT、AST水平也下降;水飞蓟宾对CYP450、CYP2E1无影响,但能使TIMP-1、TIMP-2、ALT、AST含量下降。结论:西咪替丁、水飞蓟宾均能改善NASH大鼠肝功水平,西咪替丁通过抑制CYP450起作用,水飞蓟宾对CYP450无作用。     

Altered cytochrome P450 and P-glycoprotein levels in rats during simulated weightlessness

BACKGROUND: In order to investigate the effects of simulated weightlessness on drug metabolism, liver, kidney, and small intestine, microsomal proteins from tail-suspended rats were analyzed to determine cytochrome P450 (CYP) and P-glycoprotein levels following varying durations of tail-suspension. HYPOTHESIS: P-glycoprotein and CYP levels would both decrease similar to previous findings from actual spaceflight data. METHODS: Six groups of four Sprague-Dawley rats each were tail-suspended for up to 21 d; CYP and P-glycoprotein levels in the liver, kidney and small intestine were then measured by Western blotting. The results were compared with a control group of unsuspended rats. RESULTS: Our data showed there were significant changes in the levels of hepatic CYP2C11, 2E1, 4A1, and P-glycoprotein and significant changes in the levels of P-glycoprotein and CYP4A1 in the kidney. However, there were no significant changes detected in the levels of CYP3A2 in the liver or small intestine. CONCLUSIONS: We conclude that simulated weightlessness, using the tail-suspended rat model, showed significant suppressive effects on levels of CYP2C11, 2E1, and P-glycoprotein in the liver and CYP4A1 in the kidney, while demonstrating no significant effect on the levels of CYP3A2 in the liver or small intestine. Thus, generalized predictions on the effect of simulated microgravity on drug metabolism cannot be made and the overall effect of spaceflight on individual enzymes should be investigated.     

Phase I metabolic profiling of the synthetic cannabinoids THJ-018 and THJ-2201 in human urine in comparison to human liver microsome and cytochrome P450 isoenzyme incubation

International Journal of Legal Medicine - Despite the increasing relevance of synthetic cannabinoids as one of the most important classes within “New Psychoactive Substances”, there is...     

Influence of gamma-rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs

PURPOSE: Phenothiazine drugs have been found to sensitize hypoxic cancer cells while offering protection to normal cells. Since phenothiazines are known to induce the cytochrome P450 system, its radiomodulation by phenothiazines has been examined. MATERIALS AND METHODS: Mice were administered phenothiazines intraperitoneally and irradiated with different doses of gamma-rays at 1.38 Gy/min. The activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase, the content of cytochrome P450 and b5, the extent of lipid peroxidation as well as the activities of LDH, XO, SOD, GST and DTD were determined in the liver. RESULTS: The levels of different components of the cytochrome P450 system and antioxidant enzymes were enhanced up to 5 Gy and decreased thereafter. However, a progressive increase was noticed in peroxidative damage and the activities of LDH and XO. Administration of phenothiazines enhanced the radiation effect on components of the cytochrome P450 system (except NADH-cytochrome b5 reductase) and the activities of SOD, GST and DTD. Concomitantly, phenothiazines inhibited lipid peroxidation, LDH and XO. CONCLUSIONS: Activation of the cytochrome P450 system by phenothiazines leading to the enhancement of antioxidant potential of animals and free-radical scavenging are attributes of the radioprotective action of phenothiazines.     

In vivo study on the roles of cytochrome P450 enzymes for metabolism of 3,4-methylenedioxymethamphetamine (Ecstasy) in rats

Some major metabolic pathways of 3,4-methylenedioxymethamphetamine (MDMA) have been shown to be dependent on cytochrome P450 (CYP) isozymes by in vitro studies. The aim of this study was to clarify the roles of these CYP enzymes for in vivo metabolism of MDMA with respect to two pathways using rats: N-demethylation of MDMA to 3,4-methylenedioxyamphetamine (MDA) and O-demethylenation of MDMA to 3,4-dihydroxymethamphetamine (HHMA)followed by O-methylation to 4-hydroxy-3-methoxymethamphetamine (HMMA). Rats were pretreated with phenobarbital (PB, 80 mg/kg i.p.) or β-naphthoflavone (BNF, 80 mg/kg i.p.) once a day for 3 days before administration of MDMA (10 mg/kg i.p.). Metabolic changes were monitored by measuring the urinary excretion of MDMA and its metabolites. Twenty-four hours after MDMA administration, MDA in rat urine was significantly decreased by 43% and 70%, and HMMA was significantly increased by 33% and 64% in urine samples from PB-pretreated and BNF-pretreated rats, respectively, as compared with the control values. Testosterone 6β-hydroxylase (CYP3A), pentoxyresorufin O-dealkylase (CYP2B1), ethoxyresorufin O-deethylase (CYP1A1), and methoxyresorufin O-demethylase (CYP1A2) activities were increased 2–6 fold in both PB-pretreated and BNF-pretreated rat liver microsomes sampled at 24 h after MDMA administration as compared with the control values. These results suggest that PB-induced and BNF-induced CYP enzymes have inhibitory effects on N-demethylation of MDMA to MDA in vivo in rats. If HHMA is the precursor of HMMA in rats, there is a possibility that the O-demethylenation of MDMA to HHMA is increased by the induced CYP enzymes. The decreased urinary concentration of MDMA and very low percent recoveries of MDA, HMMA, and (4-hydroxy-3-methoxyphenyl)acetone (HMPA) in the inducer-pretreated groups suggest that other metabolic pathways of MDMA exist and are activated under the present experimental conditions.     

福辛普利对大鼠肝纤维化的影响

目的 研究血管紧张素转换酶抑制剂福辛普利抗大鼠肝纤维化的作用.方法 雄性清洁级SD大鼠40只,随机分成5组:阴性对照组(n=5),腹腔注射植物油,每日单蒸水灌胃;模型组(n=5),腹腔注射CCl4,每日单蒸水灌胃;阳性对照组(n=10),造模方法同模型组,每日用秋水仙碱0.2mg/kg灌胃;福辛普利小剂量组(n=10)...     

The relevance of cytochrome P450 polymorphism in forensic medicine and akathisia-related violence and suicide

Adverse drug reactions and interactions are among the major causes of death in the United States. Antidepressants have been reported as causing suicide and homicide and share the class attribute of frequently producing akathisia, a state of severe restlessness associated with thoughts of death and violence. Medical examiners can now identify some pharmacogenetic interactions that cause drugs, deemed safe for most, to be lethal to others. Such deaths do not yet include medication-induced, akathisia-related suicides and homicides. An extrapyramidal side effect, akathisia is a manifestation of drug toxicity whose causes lie, inter alia, in drugs, doses, and co-prescribed medications that inhibit and compete for metabolizing enzymes, which may themselves be defective. In this paper, we report our investigation into adverse drug reactions/interactions in three persons who committed homicide, two also intending suicide, while on antidepressants prescribed for stressful life events. Their histories of medication use, adverse reactions and reasons for changes in medications are presented. DNA samples were screened for variants in the cytochrome P450 gene family; that produce drug metabolizing enzymes. All three cases exhibit genotype-based diminished metabolic capability that, in combination with their enzyme inhibiting/competing medications, decreased metabolism further and are the likely cause of these catastrophic events.     

芳香化酶P450与环氧化酶-2在子宫内膜异位症和子宫腺肌病中的表达及意义

目的研究细胞色素芳香化酶P450（P450arom）和环氧化酶-2（COX-2）在子宫内膜异位症（EMs）和子宫腺肌病（AM）在位和异位内膜中的表达及相关性。方法应用免疫组化Envision法和半定量逆转录聚合酶链反应（RT-PCR）技术检测正常子宫内膜、EMs及AM的在位和异位内膜中P450arom及COX-2的蛋白与mRNA的表达,并进行相关性分析。结果P450arom和COX-2在正常子宫内膜中无表达或弱表达,二者在EMs和AM在位和异位内膜中的表达均高于正常子宫内膜,差异均有显著性意义（P〈0.05）。P450arom与COX-2在EMs和AM异位内膜中的表达均高于在位内膜,差异均有显著性意义（P〈0.05）。P450arom在EMs和AM增殖期和分泌期表达无差异（P〉0.05）。COX-2在正常子宫内膜、EMs分泌期表达高于增殖期,差异均有显著性意义（P〈0.05）,在AM表达不随月经周期变化。P450arom mRNA与COX-2mRNA在EMs中的表达水平呈正相关（r=0.964,P〈0.01）;在AM中的表达水平亦呈正相关（r=0.813,P〈0.01）。结论P450arom和COX-2在EMs和AM中呈过表达,与EMs和AM的发病相关,二者协同作用促进EMs和AM的发生发展。