ORTHO-HYDROXYPHENYLACETALDEHYDE - A MAJOR NOVEL METABOLITE OF COUMARIN FORMED BY RAT, GERBIL AND HUMAN LIVER-MICROSOMES

被引:32
作者
FENTEM, JH [1 ]
FRY, JR [1 ]
WHITING, DA [1 ]
机构
[1] UNIV NOTTINGHAM,DEPT CHEM,NOTTINGHAM NG7 2RD,ENGLAND
关键词
D O I
10.1016/0006-291X(91)91354-F
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A major novel coumarin metabolite was isolated from rat hepatic microsomal incubations by high-performance liquid chromatography. In the presence of a rat liver cytosolic fraction and NADH it was rapidly metabolized to o-hydroxyphenylethanol. The metabolite co-chromatographed with an authentic sample of o-hydroxyphenylacetaldehyde and its identity was confirmed by mass spectral analysis. The formation of o-hydroxyphenyl acetaldehyde from coumarin was NADPH-dependent. It was the major metabolite formed by rat, gerbil and human liver microsomes at a coumarin concentration of 1mM. © 1991.
引用
收藏
页码:197 / 203
页数:7
相关论文
共 23 条
[1]   LIGHT-INDUCED AND RELATED REACTIONS OF QUINONES .6. REACTIONS OF SOME PARA-QUINONES CARRYING FORMYL GROUPS [J].
BRUCE, JM ;
CREED, D .
JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1970, (05) :649-&
[2]   CRITICAL-REVIEW OF THE TOXICOLOGY OF COUMARIN WITH SPECIAL REFERENCE TO INTERSPECIES DIFFERENCES IN METABOLISM AND HEPATOTOXIC RESPONSE AND THEIR SIGNIFICANCE TO MAN [J].
COHEN, AJ .
FOOD AND COSMETICS TOXICOLOGY, 1979, 17 (03) :277-289
[3]   THE RARITY OF LIVER TOXICITY IN PATIENTS TREATED WITH COUMARIN (1,2-BENZOPYRONE) [J].
COX, D ;
OKENNEDY, R ;
THORNES, RD .
HUMAN TOXICOLOGY, 1989, 8 (06) :501-506
[4]   COMPARISON OF MONGOLIAN GERBIL AND RAT HEPATIC-MICROSOMAL MONOOXYGENASE ACTIVITIES - HIGH COUMARIN 7-HYDROXYLASE ACTIVITY IN THE GERBIL [J].
DOMINGUEZ, K ;
FENTEM, JH ;
GARLE, MJ ;
FRY, JR .
BIOCHEMICAL PHARMACOLOGY, 1990, 39 (10) :1629-1631
[5]   THE PHARMACOLOGY, METABOLISM, ANALYSIS, AND APPLICATIONS OF COUMARIN AND COUMARIN-RELATED COMPOUNDS [J].
EGAN, D ;
OKENNEDY, R ;
MORAN, E ;
COX, D ;
PROSSER, E ;
THORNES, RD .
DRUG METABOLISM REVIEWS, 1990, 22 (05) :503-529
[6]  
FENTEM J H, 1990, Human and Experimental Toxicology, V9, P329
[7]  
FENTEM JH, UNPUB
[8]  
FENTEM JH, IN PRESS XENOBIOTICA
[9]  
HAZLETON LW, 1956, J PHARMACOL EXP THER, V118, P348
[10]   THE EFFECTS OF 5,6 BENZO-[A]-PYRONE (COUMARIN) AND DEC ON FILARITIC LYMPHOEDEMA AND ELEPHANTIASIS IN INDIA - PRELIMINARY-RESULTS [J].
JAMAL, S ;
CASLEYSMITH, JR ;
CASLEYSMITH, JR .
ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY, 1989, 83 (03) :287-290