ESTABLISHMENT OF RAT PRECISION‐CUT FIBROTIC LIVER SLICE TECHNIQUE AND ITS APPLICATION IN VERAPAMIL METABOLISM (English)

Clinical and Experimental Pharmacology and Physiology

Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis. Otherwise, progressive deterioration to uncompensated cirrhosis may occur. The present study explored the characteristics of drug metabolism in fibrotic liver.

A rat precision‐cut fibrotic liver slice (PCFLS) technique was established and the metabolism of verapamil was studied employing this technique. A rat hepatic fibrosis model was successfully induced integrating complex factors that included a high‐fat diet, alcohol and CCl4. The PCFLS were incubated under different conditions and lactate dehydrogenase leakage, glutathione S‐transferase activity and 3[4,5‐dimethythiazole‐2‐yl]‐2,5‐diphenyltetrazolium bromide reduction were used as indices to assess PCFLS viability. Activities of phase I and phase II metabolizing enzymes were monitored following treatment with cytochrome P450 (CYP) inducers. Normal and fibrotic liver slices were incubated individually with 10 µmol/L verapamil. The concentration of verapamil in the medium was determined by high‐performance liquid chromatography and intrinsic clearance (Clint) was calculated on the basis of the concentration–time curve.

The results showed that the PCFLS viability remained steady throughout the 6 h of culture when the thickness of slices was 300 µm and pH of the medium was 7.0; CYP inducers (phenobarbital and ethanol) enhanced CYP2E1, CYP3A1/2 and uridine diphosphate‐glucuronate transferase (UDPGT) activities, respectively, in a time‐dependent manner. The Clint (µL/min per mg) values differed significantly between normal (9.7 ± 1.8) and fibrotic (5.6 ± 1.4) liver slices (P <� 0.01).

These results suggested that the PCFLS could remain viable for 2–6 h under appropriate conditions. The stability and inducibility of drug‐metabolizing enzymes of PCFLS were also demonstrated. Furthermore, the metabolic rate of verapamil in PCFLS was decreased. These findings add further support to the use of PCFLS as a tool to study drug metabolism and to guide clinical medication.

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Table of contents – Volume 34, Issue 5-6

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

387
MECHANISMS UNDERLYING VASORELAXANT ACTION OF ASTRAGALOSIDE IV IN ISOLATED RAT AORTIC RINGS
Zhang, Chuan / Wang, Xu‐Hui / Zhong, Mei‐Fang / Liu, Run‐Hui / Li, Hui‐Liang / Zhang, Wei‐Dong / Chen, Hong | 2007
393
PROTECTIVE ROLE OF A NOVEL ERYTHROCYTE‐DERIVED DEPRESSING FACTOR ON BLOOD VESSELS OF RENOVASCULAR HYPERTENSIVE RATS
Pang, Huan / Wen, Yun‐yi / Ma, Ning / Wang, Yu‐tang / Shi, Lei | 2007
399
THYMOQUINONE SUPPLEMENTATION PREVENTS THE DEVELOPMENT OF GENTAMICIN‐INDUCED ACUTE RENAL TOXICITY IN RATS
Sayed‐Ahmed, Mohamed M / Nagi, Mahmoud N | 2007
406
ESTABLISHMENT OF RAT PRECISION‐CUT FIBROTIC LIVER SLICE TECHNIQUE AND ITS APPLICATION IN VERAPAMIL METABOLISM
Guo, Yu / Wang, Hui / Zhang, Chun | 2007
414
STUDIES WITH KETAMINE AND ALFENTANIL FOLLOWING FREUND'S COMPLETE ADJUVANT‐INDUCED INFLAMMATION IN RATS
Edwards, Stephen R / Mather, Laurence E / Smith, Maree T | 2007
421
CYP2C19 GENOTYPE AND OMEPRAZOLE HYDROXYLATION PHENOTYPE IN CHINESE LI POPULATION
Wang, Jiu‐Hui / Li, Pei‐Qiong / Fu, Qiong‐Yao / Li, Qiu‐Xiang / Cai, Wang‐Wei | 2007
425
STRESS‐DEPENDENT INDUCTION OF PROTEIN OXIDATION, LIPID PEROXIDATION AND ANTI‐OXIDANTS IN PERIPHERAL TISSUES OF RATS: COMPARISON OF THREE STRESS MODELS (IMMOBILIZATION, COLD AND IMMOBILIZATION–COLD)
Şahın, Emel / Gümüşlü, Saadet | 2007
432
INFLUENCE OF GENDER ON OXIDATIVE STRESS, LIPID PEROXIDATION, PROTEIN DAMAGE AND APOPTOSIS IN HEARTS AND BRAINS FROM SPONTANEOUSLY HYPERTENSIVE RATS
Ren, Jun | 2007
439
CB1 RECEPTOR ACTIVATION IN THE BASOLATERAL AMYGDALA PRODUCES ANTINOCICEPTION IN ANIMAL MODELS OF ACUTE AND TONIC NOCICEPTION
Hasanein, Parisa / Parviz, Mohsen / Keshavarz, Mansoor / Javanmardi, Kazem | 2007
450
siRNA‐MEDIATED BCL‐2 AND BCL‐XL GENE SILENCING SENSITIZES HUMAN HEPATOBLASTOMA CELLS TO CHEMOTHERAPEUTIC DRUGS
Lei, Xiao‐Yong / Zhong, Miao / Feng, Lan‐Fang / Zhu, Bing‐Yang / Tang, Sheng‐Song / Liao, Duan‐Fang | 2007
457
ROSIGLITAZONE, AN AGONIST OF PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR‐GAMMA, PREVENTS CONTRALATERAL TESTICULAR ISCHAEMIA–REPERFUSION INJURY IN PREPUBERTAL RATS
Inan, Mustafa / Basaran, Umit / Dokmeci, Dikmen / Kanter, Mehmet / Yalcin, Omer / Aydogdu, Nurettin / Turan, Nesrin | 2007
462
5‐HT1A RECEPTOR AGONIST PROPERTIES OF ANTIPSYCHOTICS DETERMINED BY [35S]GTPγS BINDING IN RAT HIPPOCAMPAL MEMBRANES
Odagaki, Yuji / Toyoshima, Ryoichi | 2007
462
5-HT1A RECEPTOR AGONIST PROPERTIES OF ANTIPSYCHOTICS DETERMINED BY [35S]GTPgS BINDING IN RAT HIPPOCAMPAL MEMBRANES
Odagaki, Y. / Toyoshima, R. | 2007
467
PROTECTIVE EFFECTS OF VITAMINS C AND E AGAINST ENDOMETRIAL DAMAGE AND OXIDATIVE STRESS IN FLUORIDE INTOXICATION
Guney, Mehmet / Oral, Baha / Demirin, Hilmi / Karahan, Nermin / Mungan, Tamer / Delibas, Namik | 2007
475
LACK OF BLOOD PRESSURE SALT‐SENSITIVITY SUPPORTS A PREGLOMERULAR SITE OF ACTION OF NITRIC OXIDE IN TYPE I DIABETIC RATS
Brands, Michael W / Bell, Tracy D / Fleming, Cassandra / Labazi, Hicham / Sturgis, LaShon C | 2007
480
ENDOTOXIN‐INDUCED ACUTE LUNG INJURY AND ORGAN DYSFUNCTION ARE ATTENUATED BY PENTOBARBITAL ANAESTHESIA
Kao, Shang‐Jyh / Su, Chain‐Fa / Liu, Demeral D / Chen, Hsing I | 2007
488
THE EFFECTS OF ISOSTEVIOL AGAINST MYOCARDIUM INJURY INDUCED BY ISCHAEMIA–REPERFUSION IN THE ISOLATED GUINEA PIG HEART
Xu, Deyi / Zhang, Shuangjie / Foster, David JR / Wang, Jiping | 2007
494
DRUG‐RELATED HOSPITAL ADMISSIONS IN A GENERIC PHARMACEUTICAL SYSTEM
Zargarzadeh, AH / Emami, MH / Hosseini, F | 2007
499
OPTIMIZING DOSAGE OF KETAMINE AND XYLAZINE IN MURINE ECHOCARDIOGRAPHY
Xu, Qi / Ming, Ziqiu / Dart, Anthony M / Du, Xiao‐Jun | 2007
508
WRITING INTELLIGIBLE ENGLISH PROSE FOR BIOMEDICAL JOURNALS
Ludbrook, John | 2007
515
SLOW INOTROPIC RESPONSE OF INTACT LEFT VENTRICLE TO SUDDEN DILATION CRITICALLY DEPENDS ON A MYOCARDIAL DIALYSABLE FACTOR
Tucci, Paulo JF / Faber, Cristiano N / Santos, Leonardo dos / Antonio, Ednei L | 2007
517
ROLE OF XANTHINE OXIDASE IN DEXAMETHASONE‐INDUCED HYPERTENSION IN RATS
Ong, Sharon LH / Vickers, Janine J / Zhang, Yi / McKenzie, Katja US / Walsh, Claire E / Whitworth, Judith A | 2007
520
QUANTITATIVE CHARACTERIZATION OF A REPEATED ACUTE JOINT INFLAMMATION MODEL IN RATS
Peter‐Szabo, Mihaly / Kekesi, Gabriella / Nagy, Edit / Sziver, Edit / Benedek, Gyorgy / Horvath, Gyongyi | 2007
527
INTRODUCTION
Hannan, Anthony J | 2007
528
PROGENITOR CELLS AND ADULT NEUROGENESIS IN NEURODEGENERATIVE DISEASES AND INJURIES OF THE BASAL GANGLIA
Curtis, Maurice A / Eriksson, Peter S / Faull, Richard LM | 2007
533
REGULATORS OF ADULT NEUROGENESIS IN THE HEALTHY AND DISEASED BRAIN
Grote, Helen E / Hannan, Anthony J | 2007
546
5‐HT7, NEUROGENESIS AND ANTIDEPRESSANTS: A PROMISING THERAPEUTIC AXIS FOR TREATING DEPRESSION
Nandam, L Sanjay / Jhaveri, Dhanisha / Bartlett, Perry | 2007

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