Biomedical subjects

Su Zeng

Publications and source records attributed to Su Zeng.

42 records · Page 3Linked to original sources

PubMed2003

[Development of a K562 multidrug-resistant cell line and study on proteins with altered expression].

In an attempt to study the whole protein expression alterations of tumer cells after becoming multidrug-resistant, which may provide useful information on new drug target identification, an adriamycin-resistant variant of the human leukemia cell line K562 (K562/ADR) was developed in vitro by continuous exposure to adrimycin. MTT assay was used to determine IC50 of K562/ADR cells to adriamycin (ADR), cisplatin (DDP), 5-fluorouracil (5-FU) and vincristin (VCR). The total proteins of K562 and K562/ADR were separated by two-dimensional gel electrophoresis and visualized by silver staining. Proteins with significant expression alterations were selected and their peptide mass fingerprints (PMFs) were obtained by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The PMFs were used to search NCBInr database by AutoMS-Fit software. The results showed that K562/ADR cell demonstrated cross-resistance to other antineoplastic drugs. The IC50 of K562/ADR cells to ADR, DDP, 5-FU, VDR were much higher than those of K562. The proteins differentially expressed in the two cell lines were identified as cell cycle-related proteins, zinc finger protein 165, etc. These proteins are involved in cell cycling and transcription regulation, whose expression alterations may contribute to the multidrug resistant phenotype of K562/ADR cells.

Antineoplastic Agents↗

PubMed2003

[Ginkgo flavones in in vitro metabolism and its clinical application].

AIM: To develop a method for assaying Ginkgo flavones in rat hepatical microsome. METHODS: Quercetin, isorhamnetin and keampferol were added to microsome incubate and incubated for a given time then extracted with ether-acetone. After evaporated, the residue was reconstituted with 100 microL of phosphate buffer solution (pH 2.0)-tetrahydrofuran-methanol-isopropanol (60:15:10:20). An aliquot of 20 microL was injected into the HPLC system. According to the result of estimate by means of HPLC, the results of metabolism of Ginkgo flavones in different conditions was compared. RESULTS: The assay was linear over the rang of 0.2-8 mg.L-1 for Ginkgo flavones. The limit of quantification was 0.1 mg.L-1 (n = 3). The recoveries of three components of Ginkgo flavones were 99.9%-113.8% for quercetin (RSD < 0.8%), 100.8%-117.3% for isorhamnetin (RSD < 1.9%) and 100.7%-116.5% for keampferol (RSD < 1.03%, n = 5). CONCLUSION: The method is simple, fast and accurate. It can be used for investigation of the metabolism of Ginkgo flavones.

Animals↗

PubMed2002

Analysis of enantiomers of chiral phenethylamine drugs by capillary gas chromatography/mass spectrometry/flame-ionization detection and pre-column chiral derivatization.

Several important chiral phenethylamine agents such as mexiletine, fenfluramine, amphetamine, methamphetamine and N-n-propylamphetamine show stereoselective disposition in humans and large differences in therapeutic relevance and toxicity. To analyze the enantiomers of chiral amine drugs, stereoselective methods were developed to separate those enantiomers on an achiral capillary gas chromatography by pre-column chiral derivatization with S-(-)-N-(fluoroacyl)-prolyl chloride. The stereoselectivity and sensitivity can be improved by chiral derivatization. The methods established offer enantioselective, simple, flexible and economic approaches for the analysis of chiral amine drug enantiomers in biological fluids. The methods have been used to determine S-(+)-methamphetamine in human forensic samples and to analyze enantiomers of amphetamine and fenfluramine in rat liver microsomes.

Chromatography, Gas↗

PubMed2002

[Enatiomeric separation of beta-blocking agents and analogs]

OBJECTIVE: To evaluate enantiomeric separation methods for beta-blocking agents and analogs. METHODS: Enantiomeric separation of racemates of 11 beta-blocking agents and their analogs was performed using chiral stationary phases and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). RESULTS: These beta -blocker racemates were separated into enantiomers in one or several chormatographic states such as propranolol, bisoprolol, metoprolol, celiprolol, carvedilol, sotalol, propafenone, ephedrine, and zomitriptan. Temperature had a significant effect on the resolution of the drugs when using chiralcel OD. Lower temperatures were associated with higher resolutions. CONCLUSION: When separating beta-blocking agents and their analogs, Chiralcel OD, Chiralpak AD, Chiral stationary phases and GITC chiral derivative reagents have complementary functions.

Journal Article↗

PubMed2002

Effects of stereochemical aspects on drug interaction in pharmacokinetics.

Recent literatures on enantiomer/enantiomer and enantiomer/coadministered drug interactions in pharmacokinetics were reviewed. The clinical significance of introducing the concept of stereoselectivity into pharmacokinetic interaction study cannot be overestimated, such as avoiding interaction-based adverse reactions, increasing therapeutic index, resolving the apparent anomaly in the plasma concentration-effect relationship and providing starting point of investigation into drug disposition, etc. Study in this respect should be enhanced.

Drug Interactions↗

PubMed2000

Stereoselective propranolol metabolism in two drug induced rat hepatic microsomes.

AIM:To study the influence of inducers BNF and PB on the stereoselective metabolism of propranolol in rat hepatic microsomes.METHODS:Phase I metabolism of propranolol was studied by using the microsomes induced by BNF and PB and the non induced microsome as the control.The enzymatic kinetic parameters of propranolol enantiomers were calculated by regression analysis of Lineweaver-Burk plots. Propranolol concentrations were assayed by HPLC.RESULTS:A RP-HPLC method was developed to determine propranolol concentration in rat hepatic microsomes. The linearity equations for R(+)propranolol and S(-) propranolol were A = 705.7C+311.2C (R = 0.9987) and a = 697.2C+311.4C (R = 0.9970) respectively. Recoveries of each enantiomer were 98.9%, 99.5%, 101.0% at 60&mgr;mol/L, 120&mgr;mol/L, 240&mgr;mol/L respectively. At the concentration level of 120&mgr;mol/L, propranolol enantiomers were metabolized at different rates in different microsomes. The concentration ratio R(+)/S(-) of control and PB induced microsomes increased with time, whereas that of microsome induced by BNF decreased. The assayed enzyme parameters were: 1. Km. Control group: R(+)30 plus minus 8, S(-)18 plus minus 5; BNF group: R(+)34 plus minus 3, S(-)39 plus minus 7; PB group: R(+)38 plus minus 17, S(-)36 plus minus 10. 2. Vmax. Control group: R(+)1.5 plus minus 0.2, S(-)2.9 plus minus 0.3; BNF group: R(+)3.8 plus minus 0.3, S(-)3.3 plus minus 0.5; PB group: R(+)0.07 plus minus 0.03, S(-)1.94 plus minus 0.07. 3. Clint. Control group: R(+)60 plus minus 3, S(-)170 plus minus 30; BNF group: R(+)111.0 plus minus 1, S(-) 84 plus minus 5; PB group: R(+)2.0 plus minus 2, S(-)56.0 plus minus 1. The enzyme parameters compared with unpaired t tests showed that no stereoselectivity was observed in enzymatic affinity of three microsomes to enantiomers and their catalytic abilities were quite different and had stereoselectivities.Compared with the control, microsome induced by BNF enhanced enzyme activity to propranolol R(+)enantiomer, and microsome induced by PB showed less enzyme activity to propranolol S(-)enantiomer which remains the same stereoselectivities as that of the control.CONCLUSION:Enzyme activity centers of the microsome were changed in composition and regioselectivity after the induction of BNF and PB, and the stereoselectivities of propranolol cytochrome P450 metabolism in rat hepatic microsomes were likely due to the stereoselectivities of the catalyzing function in enzyme.CYP1A subfamily induced by BNF exhibited pronounced contribution to propranolol metabolism with stereoselectivity to R(+)enantiomer.CYP2B subfamily induced by PB exhibited moderate contribution to propranolol metabolism, but still had the stereoselectivity of S(-)enantiomer.

Journal Article↗