Identification of o-hydroxyphenylacetaldehyde as a major metabolite of coumarin in rat hepatic microsomes.
The metabolism of [3-14C]coumarin has been studied in hepatic microsomes from control (corn-oil treated) and Aroclor 1254-treated (100 mg/kg body weight/day, 5 days, ip) rats. [3-14C]Coumarin metabolites in incubate extracts were separated by HPLC and identified by comparison with the retention times of known coumarin metabolites. The major product produced by incubation of 0.25-2.5 mM-[3-14C]coumarin with both control and Aroclor 1254-induced hepatic microsomes was a novel coumarin metabolite. This novel metabolite was extracted from pooled microsomal incubations, purified by semi-preparative HPLC and identified by mass spectrometry as o-hydroxyphenylacetaldehyde (o-HPA). Some possible pathways for the formation of o-HPA from coumarin are proposed.
Lake
B G
BG
BIBRA Toxicology International, Carshalton, Surrey, UK.
Osborne
D J
DJ
Walters
D G
DG
Price
R J
RJ
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D003374:Coumarins; D020111:Chlorodiphenyl (54% Chlorine); D009249:NADP; C070647:2-hydroxyphenylacetaldehyde; C030123:coumarin; D000079:Acetaldehyde