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121.
The present cell culture study investigated the effect of Ginkgo biloba extract pretreatment on acetaminophen toxicity and assessed the role of ginkgolide A and cytochrome P450 3A (CYP3A) in hepatocytes isolated from adult male Long-Evans rats provided ad libitum with a standard diet. Acetaminophen (7.5-25 mM for 24 h) conferred hepatocyte toxicity, as determined by the lactate dehydrogenase (LDH) assay. G. biloba extract alone increased LDH leakage in hepatocytes at concentrations > or =75 mug/ml and > or =750 mug/ml after a 72 h and 24 h treatment period, respectively. G. biloba extract (25 or 50 mug/ml once every 24 h for 72 h) potentiated LDH leakage by acetaminophen (10 mM for 24 h; added at 48 h after initiation of extract pretreatment). The effect was confirmed by a decrease in [(14)C]-leucine incorporation. At the level present in a modulating concentration (50 mug/ml) of the extract, ginkgolide A (0.55 mug/ml), which increased CYP3A23 mRNA levels and CYP3A-mediated enzyme activity, accounted for part but not all of the potentiating effect of the extract on acetaminophen toxicity. This occurred as a result of CYP3A induction by ginkgolide A because triacetyloleandomycin (TAO), a specific inhibitor of CYP3A catalytic activity, completely blocked the effect of ginkgolide A. Ginkgolide B, ginkgolide C, ginkgolide J, quercetin, kaempferol, isorhamnetin, and isorhamnetin-3-O-rutinoside did not alter the extent of LDH leakage by acetaminophen. In summary, G. biloba pretreatment potentiated acetaminophen toxicity in cultured rat hepatocytes and ginkgolide A contributed to this novel effect of the extract by inducing CYP3A. 相似文献
122.
槲皮素逆转白血病细胞株HL-60/ADM多药耐药的研究 总被引:7,自引:1,他引:6
目的探讨槲皮素(Que)逆转白血病细胞多药耐药在膜转运蛋白方面的机制。方法通过四唑蓝体外药敏法,检测Que对柔红霉素(DNR)的增敏作用,并以不同浓度作用于HL-60/ADM耐药株及相应敏感株HL-60;运用逆转录多聚酶链式反应和流式细胞术,检测HL-60/ADM和HL-60细胞株多药耐药相关基因1(MRP1)及其膜蛋白产物MRP1蛋白的表达情况;借助激光共聚焦显微镜,观察DNR在亚细胞水平的分布变化。结果20~40μmol/L终浓度的Que在体外能明显提高DNR对HL-60/ADM耐药株的敏感性,并能下凋MRP1基因及其膜蛋白产物MRP1的表达,使DNR回归于细胞核内,从而逆转多药耐药,而且对细胞本身无明显毒性作用。结论Que有可能成为蒽环类药物治疗白血病的有效且低毒的化疗增敏剂。 相似文献
123.
Mina Bakhshaeshi Arash Khaki Fatemeh Fathiazad Amir Afshin Khaki Elham Ghadamkheir 《Asian Pacific Journal of Tropical Biomedicine》2012,2(7):528-531
Objective
To study the role of Quercetin in streptozotocin-induced diabetes in rats.Methods
Wistar male rat (n=40) were allocated into three groups, control group (n=10) and Quercetin (QR) group received 15 mg/kg (IP) QR, (n=10), and diabetic group that received 55 mg/kg (IP) streptozotocin (STZ) (n=20) which was subdivided to two groups of 10; STZ group and treatment group. Treatment group received 55 mg/kg (IP) STZ plus 15 mg/kg QR, daily for 4 weeks, respectively; however, the control group just received an equal volume of distilled water daily (IP). Diabetes was induced by a single (IP) injection of streptozotocin (55 mg/kg). Animals were kept in standard condition. Twenty-eight days after inducing diabetic, 5 mL blood were collected for TAC, MDA and Ox-LDL levels and liver tissues of rat in whole groups were removed then prepared for apoptosis analysis by Tunel method.Results
Apoptotic cells significantly decreased in group that has received 15 mg/kg (IP) Quercetin (P<0.05) in comparison to experimental groups (P<0.05).Conclusions
Since in our study 15 mg/kg (IP) Quercetin have significantly Preventive effect on liver cells damages by reducing number of apoptotic cells in Liver, so it seems that using it can be effective for treatment in diabetic rat. 相似文献124.
Montenegro L Carbone C Maniscalco C Lambusta D Nicolosi G Ventura CA Puglisi G 《International journal of pharmaceutics》2007,336(2):257-262
Quercetin-3-O-acyl esters (I-VI) were synthesized and their usefulness as quercetin topical prodrugs was evaluated. Quercetin esters were assayed to determine their water stability and solubility, their susceptibility to undergoing enzymatic hydrolysis and their permeation through excised human skin. Quercetin ethyl (I) and hexyl (IV) esters proved poorly stable in aqueous media and they were not assayed further. Among the derivatives tested, quercetin propyl (II) and butyl (III) esters were more water-soluble than the parent drug. Esters II, III and V were readily hydrolyzed by human plasma and esters II and III penetrated excised human skin better than quercetin from aqueous saturated solutions. On the basis of the results obtained, esters II and III could be regarded as promising quercetin topical prodrugs. 相似文献
125.
We previously isolated quercetin 3-O-beta-(2"-galloyl)-rhamnopyranoside (QGR), a quercitrin gallate, from aerial parts of Persicaria lapathifolia (Polygonaceae) to prevent superoxide produc tion in monocytes from venous blood of healthy human donors. In this study, effects of QGR and its building moieties (quercitrin, quercetin and gallic acid) on the production of peroxyni trite, a coupling oxidant between superoxide and nitric oxide (NO) radicals, were investigated in zymosan A-stimulated macrophages RAW 264.7. The QGR, quercitrin and quercetin inhib ited peroxynitrite production in dose-dependent manners with IC50 values of 2.1 microM, 24.5 microM and 5.1 microM, respectively, but gallic acid even at 100 microM was inactive. QGR also inhibited both zymosan A- and phorbol 12-myristate 13-acetate-induced superoxide productions with IC50 values of 3.2 microM and 4.7 microM, respectively. However, QGR affected neither zymosan A-induced NO production nor inducible NO synthase synthesis. Taken together, QGR could inhibit peroxynitrite production by blocking superoxide production without affecting NO production. Finally, this study could provide a pharmacological potential of QGR in the oxidative stress-implicated disorders. 相似文献
126.
Oliveira-Brett AM Paquim AM Diculescu VC Piedade JA 《Medical engineering & physics》2006,28(10):963-970
A DNA electrochemical biosensor is an integrated receptor-transducer device. The most important step in the development and manufacture of a sensitive DNA-biosensor for the detection of DNA-drug interactions is the immobilization procedure of the nucleic acid probe on the transducer surface. Magnetic A/C Mode atomic force microscopy (MAC Mode AFM) images in air were used to characterize two different procedures for immobilising nanoscale double-stranded DNA (dsDNA) surface films on carbon electrodes. Thin film dsDNA layers presented holes in the dsDNA film that left parts of the electrode surface uncovered while thicker films showed a uniform and complete coverage of the electrode. These two procedures for preparing dsDNA-biosensors were used to study the influence of reactive oxygen species (ROS) in the mechanism of DNA damage by quercetin, a flavonoid, and adriamycin, an anthracycline anticancer drug. The study of quercetin–DNA interactions in the presence of Cu(II) ions indicated that the formation of a quercetin–Cu(II) complex leads to the formation of ROS necessary to react with DNA, disrupting the helix and causing the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). Reduced adriamycin radicals are able to directly cause oxidative damage to DNA, generating 8-oxodGuo and ROS are not directly involved in this genomic mutagenic lesion. 相似文献
127.
128.
目的:建立以高效液相色谱(HPLC)法测定不同产地叶下珠中槲皮素含量的方法。方法:色谱柱为ZorbaxSB-C18(250mm×4.6mm,5.0μm),流动相为乙腈-0.2%磷酸(30:70),流速为1mL·min-1,紫外检测波长为370nm。结果:槲皮素进样量在0.05~0.40μg范围内与峰面积积分值呈良好的线性关系(r=0.9999);平均回收率为102.23%,RSD=1.87%(n=6)。云南产的叶下珠中槲皮素的含量最高。结论:本方法简便、快速、准确,可为正确选择叶下珠原料及其综合开发提供科学依据。 相似文献
129.
目的:建立以高效液相色谱法测定菝葜提取物中槲皮素含量的方法。方法:色谱柱为Kromasil 100-5C18(250mm×4.6mm,5μm),检测波长为370nm,流动相为甲醇-0.4%磷酸(49∶51),柱温为35℃,流速为1.0mL·min-1。结果:槲皮素检测浓度在0.041~0.410μg范围内与峰面积积分值呈良好的线性关系(r=0.9997);平均回收率为97.81%,RSD=1.04%(n=6)。结论:本方法简便、准确,可作为菝葜提取物中槲皮素的含量测定方法。 相似文献
130.
K.-C. Choi W.-T. Chung J.-K. Kwon J.-Y. Yu Y.-S. Jang S.-M. Park S.-Y. Lee J.-C. Lee 《Food and chemical toxicology》2010
Aflatoxin B1 (AFB1)-mediated hepatic damage is involved in production of AFB1-8,9-epoxide-bound DNA adducts and this is also affected by a pro-oxidant potential of the toxin. In this study we investigated the effects of quercetin on AFB1-treated HepG2 cells. We also examined the biochemical mechanisms associated with the effects of quercetin on AFB1-mediated liver damage in mice. Our results revealed that quercetin and isorhamnetin inhibit production of reactive oxygen species and cytotoxicity, and block the decrease of reduced glutathione (GSH) levels in AFB1-treated HepG2 cells. Isorhamnetin have inhibitory ability on lipid peroxidation stronger than quercetin in the cells. Oral supplementation with quercetin decreased serum lactate dehydrogenase levels, increased hepatic GSH levels and superoxide dismutase activity, and reduced lipid peroxidation in both the liver and kidney in AFB1-treated mice. However, quercetin did not show a significant reduction on serum levels of alkaline phosphate, alanine aminotransferase and aspartate aminotransferase that were increased in AFB1-treated mice. HPLC analysis revealed that quercetin in plasma is mainly present as glucoronides and/or sulfates of quercetin. Collectively, it is suggested that quercetin does not directly protect against AFB1-mediated liver damage in vivo, but exerts a partial role in promoting antioxidative defense systems and inhibiting lipid peroxidation. 相似文献