Enhancement of the predicted drug hepatotoxicity in gel entrapped hepatocytes within polysulfone-g-poly (ethylene glycol) modified hollow fiber

被引：18

作者：

Shen, Chong ^{[1
]}

Zhang, Guoliang ^{[2
]}

Meng, Qin ^{[1
]}

机构：

[1] Zhejiang Univ, Dept Chem & Biol Engn, Hangzhou 310027, Zhejiang, Peoples R China

[2] Zhejiang Univ Technol, Inst Biol & Environm Engn, Hangzhou 310012, Zhejiang, Peoples R China

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 2010年 / 249卷 / 02期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Drug adsorption; Gel entrapped hepatocytes; Hollow fiber; Hepatotoxicity; Cell function; RAT HEPATOCYTES; CELL-CULTURE; ADSORPTION; LIVER; ENTRAPMENT; MEMBRANES; BIOREACTOR; MORPHOLOGY; MONOLAYER; CLOZAPINE;

D O I：

10.1016/j.taap.2010.08.028

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Collagen gel-based 3D cultures of hepatocytes have been proposed for evaluation of drug hepatotoxicity because of their more reliability than traditional monolayer culture. The collagen gel entrapment of hepatocytes in hollow fibers has been proven to well reflect the drug hepatotoxicity in vivo but was limited by adsorption of hydrophobic drugs onto hollow fibers. This study aimed to investigate the impact of hollow fibers on hepatocyte performance and drug hepatotoxicity. Polysulfone-g-poly (ethylene glycol) (PSf-g-PEG) hollow fiber was fabricated and applied for the first time to suppress the drug adsorption. Then, the impact of hollow fibers was evaluated by detecting the hepatotoxicity of eight selected drugs to gel entrapped hepatocytes within PSf and PSf-g-PEG hollow fibers, or without hollow fibers. The hepatocytes in PSf-g-PEG hollow fiber showed the highest sensitivity to drug hepatotoxicity, while those in PSf hollow fiber and cylindrical gel without hollow fiber underestimated the hepatotoxicity due to either drug adsorption or low hepatic functions. Therefore, the 3D culture of gel entrapped hepatocytes within PSf-g-PEG hollow fiber would be a promising tool for investigation of drug hepatotoxicity in vitro. (c) 2010 Elsevier Inc. All rights reserved.

引用

页码：140 / 147

页数：8

共 44 条

[1] Cell morphology, albumin secretion and glutathione S-transferase expression in collagen gel sandwich and immobilization cultures of rat hepatocytes [J].

Beken, S ;

Tytgat, T ;

Pahernik, S ;

Koebe, HG ;

Vercruysse, A ;

Rogiers, V .

TOXICOLOGY IN VITRO, 1997, 11 (05) :409-&

[2] The CYP2E1-humanized transgenic mouse:: Role of CYP2E1 in acetaminophen hepatotoxicity [J].

Cheung, C ;

Yu, AM ;

Ward, JM ;

Krausz, KW ;

Akiyama, TE ;

Feigenbaum, L ;

Gonzalez, FJ .

DRUG METABOLISM AND DISPOSITION, 2005, 33 (03) :449-457

[3] Induction of hepatic cytochrome P4502E1 in rats by acetylsalicylic acid or sodium salicylate [J].

Damme, B ;

Darmer, D ;

Pankow, D .

TOXICOLOGY, 1996, 106 (1-3) :99-103

[4] Use of hydrodynamic and electrical measurements to determine protein fouling mechanisms for microfiltration membranes with different structures and materials [J].

de Lara, R. ;

Benavente, J. .

SEPARATION AND PURIFICATION TECHNOLOGY, 2009, 66 (03) :517-524

[5] Effect of phenobarbital on 7-ethoxycoumarin-O-deethylase and microsomal epoxide hydrase activities in collagen gel cultures of rat hepatocytes [J].

deSmet, K ;

Callaerts, A ;

Vercruysse, A ;

Rogiers, V .

TOXICOLOGY IN VITRO, 1997, 11 (05) :459-463

[6] Present and future developments in hepatic tissue engineering for liver support systems - State of the art and future developments of hepatic cell culture techniques for the use in liver support systems [J].

Diekmann, Sonja ;

Bader, Augustinus ;

Schmitmeier, Stephanie .

CYTOTECHNOLOGY, 2006, 50 (1-3) :163-179

[7] Glucuronidation and Covalent Protein Binding of Benoxaprofen and Flunoxaprofen in Sandwich-Cultured Rat and Human Hepatocytes [J].

Dong, Jennifer Q. ;

Smith, Philip C. .

DRUG METABOLISM AND DISPOSITION, 2009, 37 (12) :2314-2322

[8] 3D hepatocyte monolayer on hybrid RGD/galactose substratum [J].

Du, Yanan ;

Chia, Ser-mien ;

Han, Rongbin ;

Chang, Shi ;

Tang, Huihuan ;

Yu, Hanry .

BIOMATERIALS, 2006, 27 (33) :5669-5680

[9] Fractionation of natural and model egg-white protein solutions with modified and unmodified polysulfone UF membranes [J].

Ehsani, N ;

Parkkinen, S ;

Nystrom, M .

JOURNAL OF MEMBRANE SCIENCE, 1997, 123 (01) :105-119

[10] Characterization of chemically induced hepatotoxicity in collagen sandwiches of rat hepatocytes [J].

Farkas, D ;

Tannenbaum, SR .

TOXICOLOGICAL SCIENCES, 2005, 85 (02) :927-934

← 1 2 3 4 5 →