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101.
环磷酰胺对小鼠肝细胞色素P450含量的影响 总被引:2,自引:0,他引:2
目的 了解环磷酰胺 (CP)对小鼠肝细胞色素P4 5 0含量的影响。方法 小鼠腹腔注射CP 2 0mg·kg-1·d-1和CP 4 0mg·kg-1·d-1,连续 4天。以聚乙二醇法制备微粒体 ,测定肝微粒体中P4 5 0的含量。结果 CP 2 0mg·kg-1和CP 4 0mg·kg-1两组动物肝微粒体P4 5 0含量与对照组相比明显下降 (P <0 .0 5 )。结论 CP具有抑制P4 5 0的作用 相似文献
102.
A novel improved design for the first-generation glucose biosensor@Wang J 相似文献
103.
Moula Shah Jahan Ganapathy Vani Chennam Srinivasulu Shyamaladevi 《Hepatology research》2007,37(1):35-49
The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals. 相似文献
104.
蛇毒抗高凝状态酶、氟尿嘧啶对BEL-7404细胞作用的实验研究 总被引:1,自引:0,他引:1
目的通过蛇毒抗高凝状态酶(AHCSE)、氟尿嘧啶(5-FU)对人肝癌细胞BEL-7404(简称7404细胞)、正常LO2肝细胞(简称LO2细胞)作用的比较,研究AHCSE对肝癌的作用以及探讨其可能的作用机制。方法应用光学显微镜、透射电镜、MTT法、TUNEL、FCM等方法观察7404细胞、LO2细胞经过AHCSE、5-FU处理后,细胞形态学、生物化学等方面的变化。结果7404细胞、LO2细胞经过AHCSE、52FU处理后,发生了形态学改变;小剂量AHCSE对7404细胞具有很强的抑制作用,但对LO2细胞几乎无影响;随着剂量的加大,AHCSE对7404细胞抑制率上升不明显,但是出现对LO2细胞的抑制作用。经AHCSE作用后,7404细胞发生了凋亡,凋亡率随AHCSE浓度的增加而增加;与5-FU对7404细胞作用相似,但5-FU对LO2细胞抑制作用明显增强。结论AHCSE、5-FU对BEL-7404细胞均有很强的抑制作用,诱导细胞凋亡是其作用机制之一,AHCSE可能成为一种新的肝癌细胞凋亡的诱导剂。 相似文献
105.
代谢酶基因多态性与肿瘤的关系是近来国内外研究的热点。代谢酶基因多态性使酶的活性发生改变,是胰腺癌遗传易感性的重要机制。现综述了与胰腺癌癌变过程中有关的代谢酶基因多态性与其易感性的关系。 相似文献
106.
目的:研究短期不规则用药对幽门螺杆菌(Hp)检测结果的影响。方法:136名慢性胃炎及消化性溃疡的住院患,根据病史分为服药组即Hp检查前一周内接受过铅剂、抑酸剂治疗的患,共四例。对照组即Hp检查前未接受过药物治疗的患考,共37例。Hp检查方法包括①血清学方法;②快速尿素酶试验(RUT);③组织学方法;④13c—尿素呼气试验(13C—UBT)。结果:服药组RUT,组织学,13C—UBT方法Hp检出率分别为9.0%,21.2%,27.3%,均显低于对照组相应Hp检出率37.8%、40.5%、48.6%(P<0.01,P<0.05,P<0.05)。两组血清学方法Hp IgG、IgM阳性率各为48.5%,51.5%和54.1%,54.1%(P>0.05)。单独服用质子泵抑制剂组RUT,组织学方法Hp检出率4.0%,16.0%显低于对照组相应方法Hp检出率(P<0.01,P<0.05)。单独服用枸橼酸铋钾、H2受体拮抗剂患中各方法Hp检出率与对照组检出率无显性差异(P>0.05)。单独服用枸橼酸铋钾、H2受体拮抗剂、质子泵抑制剂三组Hp感染率14.3%、15.0%、16.0%均显低于对照组Hp感染率46.0%(P<0.05)。结论:Hp检查前短期使用铋剂、抑酸剂可导致Hp检出率下降,短期使用质子泵抑制剂可显降低RUT、组织学方法Hp检出率;各方法中快速尿素酶试验检出率最低。血清学方法检测Hp抗体不受药物影响。 相似文献
107.
Aksana I. Hubich Alexey Y. Bondar Tatsiana U. Kastsiuk Uladimir A. Kastsiuk Fyodar A. Lakhvich Mikhail V. Sholukh 《Hepatology research》2007,37(6):416-424
Aim: The cytoprotective effects of six novel synthetic prostaglandin A(2) analogs against carbon tetrachloride (CCl(4)) as a toxic agent were studied with isolated rat liver hepatocytes in vitro. Results: It was found that hepatocytes treatment with CCl(4) induced: (i) a significant increase of lactic dehydrogenase (LDH) release from cytoplasm; (ii) leakage of glutamate dehydrogenase (GDH) and acid phosphatase from mitochondria and lysosomes, respectively; (iii) 10-fold increase of trien conjugates formation; and (iv) a reduction of free SH-groups by 50%. Prostanoids U-26, U-9 and U-34 decreased cytotoxic index of CCl(4) on average by 1.5-2.0 times and were more effective than PGI(2), the well-known hepatoprotector of prostanoids type. The protective action of the prostanoids was not a cAMP- or Ca(2+)-dependent process. However, prostanoids U-26, U-9 and U-34 normalized intracellular content of SH-groups, reduced trien conjugates formation by 60-80% and strongly prevented enzyme leakage through cellular membranes. They were also able to inhibit CCl(4) effects via decreasing cytochrome P(450)2E1 activity. Conclusion: The results obtained demonstrate that prostanoids provide cytoprotective effects on liver hepatocytes through the prevention of lipid peroxidation of the plasma and the cellular membranes and maintenance of their barrier function. 相似文献
108.
单甲氧聚乙二醇化学修饰药物酶的研究进展 总被引:4,自引:0,他引:4
用单甲氧基聚乙二醉(1)化学修饰药物酶是生化药物研究开发的重要手段之一。本文综述了1化学修饰药物酶的一般方法及修饰后酶在生物和理化性质方面的变化,同时对1研究前景进行展望,并指出了尚待解决的问题。 相似文献
109.
110.
Y. BÖTTIGER P. DOSTERT M. STROLIN BENEDETTI M. BANI F. FIORENTINI M. CASATI I. POGGESTI C. ALM G. ALVAN & L. BERTILSSON 《British journal of clinical pharmacology》1996,42(6):707-711
1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l−1 and AUC (0, t h) 144 nmol l−1 h, mean MDL C max 183 nmol l−1 and AUC 2627 nmol l−1 h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C max 356 nmol l−1 and AUC 10512 nmol l−1 h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献