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Changes of lipid metabolism in plasma,liver and bile during cholesterol gallstone formation in rabbit model

World Journal of Gastroenterology 1998年第4期4卷 65-67页

作者： ZHAO JiChun1, XIAO LuJia1, ZHU Hong2, SHU Ye1 and CHENG NanSheng1Keywords cholelithiasis lipids/metabolism cholesterol/metabolism apolipoproteins/metabolism triglycerides/metabolism rabbits diseases models, animal

AIM To find out the relationship between the disturbances of lipid metabolism and the formation of cholesterol gallstones by studying the changes of lipid metabolism in plasma, liver tissue and the *** Male and female white Japanese rabbits were divided randomly into a control group (Con) and four experimental groups of 10 rabbits each fed with a diet containing 1.2% cholesterol for one, two, three and four weeks (1wk, 2wk, 3wk and 4wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL2-C, HDL3-C), very low and low density lipoprotein cholesterol (VLDL-C, LDL-C) was taken with standard enzymatic techniques. Apolipoprotein (apo) concentrations in plasma were measured by radial immunodiffusion assay for apoA1, apoB100, aopCⅡ and apoCⅢ. Total cholesterol of liver was measured by the enzymatic procedure for each animal. Bile acids, mainly glycocholate (GCA) and glycodeoxycholate (GDCA) were detected by dual wavelength thin layer *** In all the experimental groups fed with dietary cholesterol, cholesterol crystal was found in the gallbladder in 2/10 cases of the 1wk group, 4/10 of the 2wk group, 6/10 of the 3wk group and 7/10 of the 4wk group respectively. The concentration of plasma total cholesterol (TC), triglyceride (TG), phospholipid (pl), VLDL-C, LDL-C, apoB100, apoCⅡ, apoCⅢ gradually increased (P＜0.05) with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL-C, HDL2-C, HDL3-C) showed a tendency to decrease, but without statistical significance (P＞ 0.05). ApoA1 was reduced with increased feeding time of dietary cholesterol (P ＜0.05). The hepatic and biliary cholesterol increased 1-1.5 times as compared with the control group (t=5.221 and 3.445, P＜0.05). The GCA gradually decreased beginning from the control group to the 4wk group (P＜0.05).CONCLUSION Owing to the high cholesterol diet, the

关键词： metabolism rabbit lipid cholesterol

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Biosynthesis of imipramine glucuronide and characterization of imipramine glucuronidation catalyzed by recombinant UGTIA4

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Acta Pharmacologica Sinica 2006年第5期27卷 623-628页

作者： Ming-rong QIAN Su ZENG~2 Department of Pharmaceutical Analysis and Drug metabolism,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310031,China Department of Pharmaceutical Analysis and Drug metabolism College of Pharmaceutical Sciences Zhejiang University Hangzhou China

Aim:To study the profile of imipramine N~+-glucuronidation using homogenatesof recombinant uridine-5′-diphosphoglucuronosyltransferase 1A4 (UGT1A4) frombaculovirus-infected sf9 ***:Recombinant UGT1A4 was obtainedfrom sf9 cells infected with recombinant *** N~+-glucuronidewas biosynthesized by incubating imipramine with recombinant UGT1A4 andthen purified with solid-phase cartridges.A reversed phase-high pressure liquidchromatography (RP-HPLC) assay method was used to directly measure the con-centration of imipramine and its metabolite,imipramine N~+-glucuronide,withp-nitrophenol as the internal *** validated method was used to charac-terize the activity of recombinant UGT1A4 and carry out kinetic studies on imi-pramine glucuronidation in ***:The high concentration of imipramineinhibited glucuronide conjugation,so the formula V=Vmax·S/(Km+S+S~2/Ki) was usedto calculate the parameters,using MATLAB *** values of apparentKm,Ki,and Vmaxfor imipramine glucuronidation via UGT1A4 were 1.39±0.09mmol/L,6.24±0.45 mmol/L and 453.81±32.12 pmol/min per mg cell homogenate (n=3),***:As a specific substrate of UGT1A4,imipramine wasused as a convenient method to characterize the activity of recombinant UGT1A4by using ***,the profile of imipramine glucuronidation was evalu-ated by using recombinant UGT1A4 in vitro.

关键词： imipramine glucuronide uridine-5’-diphosphoglucuronosyltransferase IA4 baculovirus solid-phase extraction

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Life metabolism Travel Prize of 2023

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Life metabolism 2023年第6期2卷 1-2页

作者： Life metabolism Editorial Team UCLA Peter Tontonoz Lab Los Angeles CA 90095 USA Univ Michigan Ann Arbor MI USA Baylor Coll Med Yong Xu Lab Houston TX USA

This year(2023)is the second year of our journal,and is the first year for Life metabolism Travel *** prizes have been generously sponsored by Sable Systems China(***).The competition this year attracted 36 applications from students and postdocs from across the *** standard of the entries was really *** was therefore extremely difficult for us to make the final *** applications for 2023 Life metabolism Travel Prize were reviewed by a committee from the editorial board,and ranked based on an anonymized voting procedure.

关键词： really journal Travel

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Transport of carbamazepine and drug interactions at blood-brain barrier

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Acta Pharmacologica Sinica 2006年第2期27卷 249-253页

作者： jing-jing SUN Lin XIE Xiao-dong LIU~2 Center of Drug metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China Center of Drug metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China

Aim:To investigate the characteristics of carbamazepine(CBZ)transport anddrug interactions at the blood-brain ***:Cultured rat brain microvas-cular endothelial cells(rBMEC)were used as an in vitro model of the blood-brainbarrier(BBB).When cells became confluent,CBZ uptake over time was recordedby incubation of the cells in a medium containing 10 mg/L CBZ at 37℃.Thesteady-state uptake of CBZ by rBMEC was tested for different CBZ concentra-tions at 37℃.The effects of various agents on the steady-state uptake of CBZand efflux of CBZ from rBMEC were also ***:The uptake of CBZ byrBMEC was time-and *** steady-state uptake oc-curred at 30 rain for *** steady-state uptake was significantly in-creased(P<0.01)by treatment with *** co-administration ofcyclosporine A significantly increased the steady-state uptake of CBZ by therBMEC,whereas co-administration of olanzapine significantly decreased the up-take in a concentration-and temperature-dependent *** efflux of CBZfrom rBMEC was inhibited by ***:The transport of CBZ at the BBBis mediated by many *** specific ABC(ATP-binding cassette,ABC)efflux transporters may be involved in the transport of *** influ-ence the transport of CBZ at the BBB in different ways.

关键词： carbamazepine blood-brain barrier cyclosporine A olanzapine rat brain microvascular endothelial cells drug interaction

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Induction of diphenytriazol on cytochrome CYP1A

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Acta Pharmacologica Sinica 2004年第4期25卷 130-135页

作者： Yun-zhenHU,Tong-wei YAO2 Departmentof PharmaceuticalAnalysis and Drug metabolism, Collegeof PharmaceuticalSciences, Zhejiang University, Hangzhou 310031, China Department of Pharmaceutical Analysis and Drug metabolism College of Pharmaceutical Sciences Zhejiang University Hangzhou 310031

AIM: To study the effects of diphenytriazol on cytochrome P-450 (CYP) enzymes. METHODS: SD rats were pretreated with diphenytriazol. The catalytic activities of rat liver microsomes were determined by assaying ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-dealkylase. Phenacetin and aminopyrine were se- lected as the substrate of CYP1A and CYP2B, respectively. The concentration of remaining substrate in microso- mal incubates was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The inhi- bition of fluvoxamine or α-naphthoflavone on phenacetin metabolism was measured. RESULTS: Phenacetin was significantly metabolized in the diphenytriazol-treated microsomes and the metabolic degree increased according to the diphenytriazol-treatment days. There existed a significant correlation between the metabolic degree of phenace- tin and EROD in the microsomes pretreated with diphenytriazol. Both fluvoxamine and α-naphthoflavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (Ki) were (5.4±1.0) μmol/L and (10.4±0.5) μmol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in β- naphthoflavone group, but was significantly different from those in control group and phenobarbital group. CONCLUSION: These results reveal that diphenytriazol is a novel inducer of CYP1A.

关键词： cytochrome P-450 CYP1A diphenytriazol phenacetin liver microsomes metabolism

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Effect of baicalin and berberine on transport of nimodipine on primarycultured,rat brain microvascular endothelial cells

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Acta Pharmacologica Sinica 2007年第4期28卷 573-578页

作者： Dong-mei ZHANG Hai-yan LIU Lin XIE Xiao-dong LIU Center of Drug metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China Center of Drug metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China

Aim:To investigate whether baicalin and berberine affects the transport ofnimodipine (NMD) across the blood-brain barrier (BBB).Methods:Primary-cultured,rat brain microvascular endothelial cells (rBMEC) were used as an invitro model of the *** cells became confluent,the steady-state uptake ofNMD by rBMEC with or without baicalin and berberine was *** ef-fects of baicalin and berberine on the efflux of NMD from rBMEC were also ***:Baicalin (2-5 μg/mL) increased the uptake of NMD,and baicalin (10-20μg/mL) decreased the *** steady-state uptake of NMD was higher thanthat of control group in the presence of 0.01-1 μg/mL berberine,but was lower inthe presence of 2-10 μg/mL ***:The bidirectional effect ofbaicalin and berberine on the uptake of NMD by rBMEC was *** showed an inhibitory effect,and lower concentration demonstratedan increasing effect.

关键词： nimodipine baicalin berberine P-glycoprotein

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metabolism and metabolic inhibition of gambogic acid in rat liver microsomes

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Acta Pharmacologica Sinica 2006年第9期27卷 1253-1258页

作者： Yi-tong LIU Kun HAO Xiao-quan LIU~2 Guang-ji WANG Key Lab of Drug metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China Key Lab of Drug metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China

Aim:To study the metabolism of gambogic acid(GA)and the effects of selectivecytochrome P-450(CYP450)inhibitors on the metabolism of GA in rat liver mi-crosomes in ***:Rat liver microsomes were used to perform metabo-lism *** selective CYP450 inhibitors were used to investigate theireffects on the metabolism of GA and the principal CYP450 isofonn involved in theformation of major metabolite M1in rat liver *** of inhibition in anenzyme kinetics model were used to model the ***:GA wasrapidly metabolized to two phase I metabolites,M1and M2,in rat liver *** and M2were tentatively presumed to be the hydration metabolite and epoxidemetabolite of GA,respectively,α-Naphthoflavone uncompetitively inhibited theformation of M1while ketoconazole,sulfaphenazole,diethyl dithiocarbamate andquinidine had little or no inhibitory effects on the formation of ***:GA is rapidly metabolized in rat liver microsomes and M1is crucial for the elimina-tion of *** P-450 1A2 is the major rat CYP involved in the metabolismof GA.

关键词： gambogic acid metabolism cytochrome P-450 liver microsomes metabolic inhibition

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CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes

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Acta Pharmacologica Sinica 2007年第1期28卷 118-124页

作者： Xiao-ping ZHAO Jiao ZHONG Xiao-quan LIU~2 Guang-ji WANG Key Laboratory of Drug metabolism and Pharmacokinetics,China Pharmaceutical University Nanjing 210009,China Key Laboratory of Drug metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China

Aim:To study the metabolism of vinflunine and the effects of selective cyto-chrome P-450(CYP450)inhibitors on the metabolism of vinflunine in human ***:Individual selective CYP450 inhibitors were used to inves-tigate their effects on the metabolism of vinflunine and the principal CYP450 isoforminvolved in the formation of metabolites M1and M2in human liver ***:Vinflunine was rapidly metabolized to 2 metabolites:M1and M2in humanliver microsomes.M1and M2were tentatively presumed to be the N-oxide metabo-lite or hydroxylated metabolite and epoxide metabolite of vinflunine,*** uncompetitively inhibited the formation of M1,and competitivelyinhibited the formation of M2,while α-naphthoflavone,sulfaphenazole,diethyldithiocarbamate,tranylcypromine and quinidine bad little or no inhibitory effecton the formation of M1and ***:Vinflunine is rapidly metabolized inhuman liver microsomes,and CYP3A4 is the major human CYP450 involved in themetabolism of vinflunine.

关键词： vinflunine metabolism CYP3A4 liver microsomes

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In vitro identification of metabolites of verapamil in rat liver microsomes

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Acta Pharmacologica Sinica 2004年第1期 123-130页

作者： Lu SUN, Shu-qiu ZHANG, Da-fang ZHONG Laboratory of Drug metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China

AIM: To investigate the metabolism of verapamil at low concentrations in rat liver microsomes. METHODS: Liver microsomes of Wistar rats were prepared using ultracentrifuge method. The in vitro metabolism of verapamil was studied with the rat liver microsomal incubation at concentration of 1.0 μmol/L and 5.0 umol/L. The metabolites were separated and assayed by liquid chromatography-ion trap mass

关键词： verapamil in vitro metabolism liver microsomes high pressure liquid chromatography mass spectrometry

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Pharmacokinetics of recombinant human basic fibroblast growth factor in rabbits and mice serum and rabbits aqueous humor

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Acta Pharmacologica Sinica 2004年第8期 17-21页

作者： Qi ZHANG, Guang-ji WANG, Jian-guo SUN Center of Drug metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4 μg/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6 min for T1/2α and 7, 8, and 4.7 min for T1/2β. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 μg/kg were fitted to bi exponential equations with half-lives of 0.4, 0.6, and 0.9 min for T1/2α　and 6, 5, and 7 min for T1/2β.The AUCs were linearly correlated to doses in both cases (rrabbit=0.997, rmouse=0.999). The serum concentrations of rhbFGF were very l

关键词： fibroblast growth factor 2 pharmacokinetics enzyme-linked immunosorbent assay aqueous humor rabbits mice

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