XENOBIOTIC TRIACYLGLYCEROL FORMATION IN ISOLATED HEPATOCYTES

被引：20

作者：

MOORHOUSE, KG

DODDS, PF

HUTSON, DH

机构：

[1] SHELL RES LTD,SITTINGBOURNE RES CTR,SITTINGBOURNE ME9 8AG,KENT,ENGLAND

[2] UNIV LONDON WYE COLL,DEPT BIOCHEM & BIOL SCI,ASHFORD TN25 5AH,KENT,ENGLAND

来源：

BIOCHEMICAL PHARMACOLOGY | 1991年 / 41卷 / 08期

关键词：

D O I：

10.1016/0006-2952(91)90656-P

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The formation of neutral lipophilic metabolites from five xenobiotic carboxylic acids was studied in isolated rat hepatocytes. Oleic acid was used as a positive control. Rates of formation of lipids lay in the order: oleic acid > phytanic acid > ibuprofen > 3-phenoxybenzoic acid > indomethacin and 3-phenylbutanoic acid (rates were undetectable with the last two substrates). The process was saturable with the maximum rates at about 0.5mM substrate concentration. Supplementation of the hepatocyte system with glycerol enhanced the yields of lipid products. The hepatocytes also effectively modelled the in vivo metabolism of ibuprofen, 3-phenoxybenzoic acid and 3-phenylbutanoic acid with oxidations and classical conjugation reactions predominating over xenobiotic lipid formation.

引用

页码：1179 / 1185

页数：7

共 23 条

[1]

BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911

[2] COMPARATIVE FATE OF 2-PHENYLDODECANE IN RAT AND RAINBOW-TROUT [J].

BURKE, AB ;

HUCKLE, KR ;

MILLBURN, P .

BIOCHEMICAL SOCIETY TRANSACTIONS, 1988, 16 (01) :25-26

[3]

COLEMAN RA, 1984, J BIOL CHEM, V259, P8934

[4]

CRAYFORD JV, 1980, XENOBIOTICA, V10, P347

[5]

CROSS KE, 1988, BIOCHEM J, V255, P259

[6]

FEARS R, 1978, J LIPID RES, V19, P3

[7] LIPOPHILIC XENOBIOTIC CONJUGATES - THE PHARMACOLOGICAL AND TOXICOLOGICAL CONSEQUENCES OF THE PARTICIPATION OF DRUGS AND OTHER FOREIGN COMPOUNDS AS SUBSTRATES IN LIPID BIOSYNTHESIS [J].

FEARS, R .

PROGRESS IN LIPID RESEARCH, 1985, 24 (03) :177-195

[8]

Fry J R, 1981, Methods Enzymol, V77, P130

[9]

FRY JR, 1976, ANAL BIOCHEM, V1, P341

[10]

HAJRA AK, 1968, J BIOL CHEM, V243, P1609

← 1 2 3 →