Review Article Cytochromes P450 in fungi

Summary. The article gives an overview on the history of the discovery of P450 cytochromes and on their occurrence in nature, especially on their interactions with metabolic pathways in fungi. The significance of the P450 cytochromes in the ergosterol synthesis as well as in the inhibitory mechanisms caused by imidazole and triazole antimycotics is described is detail. Zusammenfassung. Der Artikel gibt eine Übersicht über die Entdeckungsgeschichte der P450-Cytochrome und ihr Vorkommen in der Natur. Insbesondere wird eingegangen auf das Vorkommen der P450-Cytochrome in Pilzen und ihre Interaktionen mit Stoffwechselprozessen der Pilzzellen. Die Bedeutung der P450-Cytochrome für die Ergosterol-Synthese der Pilze und für deren Hemmechanismen durch Imidazol- und Triazol-Antimykotika wird im Detail dargestellt.     

银杏叶提取物对细胞色素P450酶CYP1A2实验研究

目的　研究银杏叶提取物对大鼠细胞色素P450酶CYP1A2活性的影响。方法　银杏叶提取物10, 100mg·kg-1 2个剂量,分别经1, 5, 10天灌胃处理大鼠,以未经处理者为对照组,测定CYP1A2的酶活性。同剂量灌胃处理10天后,再单次灌胃盐酸普萘洛尔10mg·kg-1,测定普萘洛尔和N-去异丙基普萘洛尔在大鼠体内的血药浓度。结果　银杏叶提取物处理后,大鼠肝微粒体的CYP1A2酶活性显著升高,且能显著降低普萘洛尔在大鼠体内的AUC和Cmax,使N-去异丙基普萘洛尔的AUC和Cmax显著升高。结论　银杏叶提取物能显著诱导大鼠CYP1A2的酶活性,并显著影响普萘洛尔及其代谢物在大鼠体内的血药浓度。故银杏叶提取物可能影响与之同时服用、经CYP1A2代谢的药物临床疗效。     

细胞色素氧化酶CYP3A4基因突变与表型研究进展

细胞色素P4503A4在许多内源性及外源性化合物的氧化及还原代谢中起关键作用，对CYP3A4基因表达的研究具有重要意义。本文对CYP3A4基因突变及其表型特征加以总结。     

Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring.

Prochloraz is a commonly used fungicide that has shown multiple mechanisms of action in vitro. It antagonizes the androgen and the estrogen receptors, agonizes the Ah receptor, and inhibits aromatase activity. In vivo prochloraz acts antiandrogenically in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions, and increasing luteinizing hormone (LH) levels. The purpose of this study was to investigate reproductive toxic effects after exposure during gestation and lactation to prochloraz alone and a mixture of five pesticides (deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl). Prochloraz (30 mg/kg/day) or the mixture (20 mg/kg/day) was dosed to pregnant Wistar dams from gestational day (GD) 7 until postnatal day (PND) 16. Some dams were taken for cesarean section at GD 21, and others were allowed to give birth. Results showed that prochloraz and the mixture significantly reduced plasma and testicular testosterone levels in GD 21 male fetuses, whereas testicular progesterone was increased. Gestational length was increased by prochloraz. Chemical analysis of the rat breast milk showed that prochloraz was transferred to the milk. In males a significant increase of nipple retention was found, and the bulbourethral gland weight was decreased, whereas other reproductive organs were unaffected. In addition cytochrome P450 (CYP)1A activities in livers were induced by prochloraz, possibly as a result of Ah receptor activation. Behavioral studies showed that the activity level and sweet preference of adult males were significantly increased. Overall these results strongly indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis.     

CYP2E1基因多态性与肿瘤易感性研究进展

90％以上的肿瘤是由各种环境因素与职业因素引起，而大部分的外源性致癌物需经过Ⅰ相和Ⅱ相代谢酶的代谢活化才与体内生物大分子作用启动致癌过程。细胞色素P450 2E1(cytochrome P450s 2E1，CYP2E1)是人体内重要的Ⅰ相代谢酶类，参与N-亚硝胺类化合物等多种前致癌物的代谢活化过程，在体内各组织器官中有不同的表达。CYP2E1活性的表达受多种因素影响，存在多种限制性片段长度多态性，与人类肿瘤易感性间存在密切关系。     

芳香化酶P450在子宫内膜异位症中的表达及意义

目的：探讨芳香化酶P450在子宫内膜异位症发病中的作用。其阳性表达用于诊断子宫内膜异位症可行性。方法：应用免疫组化方法检测正常子宫内膜和子宫内膜异位症的在位及异位内膜芳香化酶P450的表达。结果：芳香化酶P450在正常子宫内膜无表达或弱阳性，在子宫内膜异位症的在位和异位内膜均有强表达，且增殖期高于分泌期表达，敏感度为92％，特异度为95．5％。结论：子宫内膜芳香化酶分泌增加促进子宫内膜异位症的发生，并对其诊断有重要意义。     

Influences of V5-epitope tag on the metabolic activation of AFB1 by human cytochrome P450 2A13

INTRODUCTION A flatoxin B1 (AFB1) , which is produced by Aspergillus flavus and Aspergillus parasitus, is a potent carcinogen in human and animals. Al- though AFB1 is best known as a liver carcinogen, it also induces lung tumors in animals and epidemio- logical studies show a positive association between human lung cancer occurrence and inhalation expo- sure to AFB1-containminated grain dust. As most of environmental carcinogens, metabolic activation cat- alyzed by cytochrome P450 (C…     

补肾益气方对流产大鼠胎盘孕酮生成通路的影响

目的:探讨补肾益气方对流产大鼠胎盘孕酮生成通路中相关重要上游因素低密度脂蛋白受体(LDLR)、细胞色素P450链裂解酶(P450scc)、3β-羟基类固醇脱氢酶(3β-HSD)的影响及其与孕酮(P)分泌的关系。方法:溴隐亭皮内注射法建立流产大鼠模型,分别于孕1-8 d、1-11 d灌服补肾益气方药,黄体酮肌注作为阳性对照组,采用放免法测定大鼠血清P水平;RT-PCR技术检测LDLR、P450scc、3β-HSD在不同组动物胎盘中的mRNA表达。结果:模型组LDLR、P450scc、3β-HSD mRNA表达较正常对照组明显降低;中药组及黄体酮组不同程度提高模型大鼠胎盘LDLR、P450scc、3β-HSD mRNA表达,表达强度随孕天和给药时间逐渐升高,与血P有显著相关性。结论:补肾益气方清热益气、固肾安胎,能调控胎盘滋养细胞LDLR、P450scc、3β-HSD基因表达,促进孕激素合成分泌增加,从而达到保胎维持妊娠的目的。     

抗组胺药敏感性的细胞色素P450研究进展

HP450具有细胞色素P450特征和抗组胺药敏感的双重性,它在不同的大鼠肝脏疾病模型中有明显的变化规律,与肝脏疾病的发展具有一定的相关性,在肝癌发生过程中HP450基因的转录及表达均发生了变化。HP450有可能作为诊断肝癌的新指标,在预防和治疗肝癌中可能作为一个新靶点。     

环孢素A与盐酸小檗碱合用对大鼠肝脏和小肠药物代谢酶的影响

目的:研究盐酸小檗碱(berberine chloride,Ber)与环孢素A(CsA)合用对大鼠肝脏和小肠药物代谢酶的影响.方法:采用分光光度法测定各给药组大鼠肝脏和小肠微粒体中红霉素N-脱甲基酶(ERD)、氨基比林N-脱甲基酶(ADM)和谷胱甘肽转移酶(GST)的活性.结果:Ber组和Ber CsA组能明显抑制肝微粒体中ERD、ADM和GST酶活性(P< 0.05 ),而且Ber CsA组较CsA单用组有更明显的抑制作用(P< 0.05 ).Ber CsA组还能明显抑制肠微粒体中ERD、ADM和GST酶活性(P< 0.05 ).结论:Ber与CsA合用时,能显著抑制大鼠肝脏和小肠药物代谢酶活性,这可能是Ber增加CsA血药浓度的一个重要机制.