Metabolism and absorption of auraptene (7-geranyloxylcoumarin) in male SD rats: comparison with 7-ethoxycoumarin.
We previously reported that auraptene (7-geranyloxycoumarin; AUR), a coumarin that occurs widely in citrus fruit, has been shown to be a promising cancer-preventive agent in several rodent models. However, its bioavailability and metabolism have not been investigated. In this study, we compared the metabolism characteristics of AUR with those of 7-ethoxycoumarin (ETC) in male Sprague Dawley rats. Each (500 micromol/kg body weight) was given separately by a single gastric intubation procedure, and digestive tract, liver, and kidney were removed at 1, 4, and 24 h after administration. The localization profiles of AUR and ETC in the gastrointestinal tract were similar. However, AUR, in contrast to ETC, showed significant localization in the liver from 1 to 4 h. Treatments of serum and urinary samples with glucuronidase/sulfatase led to the detection of significant amounts of umbelliferone (7-hydroxycoumarin; UMB), and serum and urinary concentrations of UMB following ETC administration were significantly higher than with AUR administration. Our results suggest that AUR, which bears a geranyloxyl side chain, has a longer life span than ETC, and this property may be associated with its previously reported chemopreventive and xenobiotics metabolizing activities.
Kuki
Wataru
W
Plant Biotechnology Laboratory, Wakayama Prefectural Federation of Agricultural Cooperatives, Wakayama, Japan.
Hosotani
Keisuke
K
Ohigashi
Hajime
H
Murakami
Akira
A
D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D018890:Chemoprevention; D002957:Citrus / Q000737:chemistry*; D003374:Coumarins / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000378:metabolism / Q000493:pharmacokinetics*
D016588:Anticarcinogenic Agents; D003374:Coumarins; D015262:Xenobiotics; C017299:7-ethoxycoumarin; C105832:aurapten