A1 Refereed original research article in a scientific journal
In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species
Authors: Juvonen RO, Pentikäinen O, Huuskonen J, Timonen J, Kärkkäinen O, Heikkinen A, Fashe M, Raunio H
Publisher: TAYLOR & FRANCIS LTD
Publication year: 2020
Journal: Xenobiotica
Journal name in source: XENOBIOTICA
Journal acronym: XENOBIOTICA
Volume: 50
Issue: 8
First page : 885
Last page: 893
Number of pages: 9
ISSN: 0049-8254
eISSN: 1366-5928
DOI: https://doi.org/10.1080/00498254.2020.1711544
Self-archived copy’s web address: https://jyx.jyu.fi/bitstream/123456789/74580/2/15834991801980327261.pdf
Abstract
Sulfonation is an important high affinity elimination pathway for phenolic compounds. In this study sulfonation of 7-hydroxycoumarin and 13 its derivatives were evaluated in liver cytosols of human and six animal species. 7-hydroxycoumarin and its derivatives are strongly fluorescent, and their sulfate conjugates are nonfluorescent at excitation 405 nm and emission 460 nm. A convenient fluorescence based kinetic assay of sulfonation was established. The sulfonation rate of most of the 7-hydroxycoumarin derivatives was low in liver cytosol of human and pig, whereas it was high with most compounds in dog and intermediate in rat, mouse, rabbit, and sheep. Sulfonation of the 7-hydroxycoumarin derivatives followed Michaelis-Menten kinetics with K-m values of 0.1-12 mu M, V-max of 0.005-1.7 mu mol/(min * g protein) and intrinsic clearance (V-max/K-m) of 0.004-1.9 L/(min * g cytosolic protein). Fluorescence based measurement of sulfonation of 7-hydroxycoumarin derivatives provides a sensitive and convenient high-throughput assay to determine sulfonation rate in different species and tissues and can be applied to evaluate sulfonation kinetics and inhibition.
Sulfonation is an important high affinity elimination pathway for phenolic compounds. In this study sulfonation of 7-hydroxycoumarin and 13 its derivatives were evaluated in liver cytosols of human and six animal species. 7-hydroxycoumarin and its derivatives are strongly fluorescent, and their sulfate conjugates are nonfluorescent at excitation 405 nm and emission 460 nm. A convenient fluorescence based kinetic assay of sulfonation was established. The sulfonation rate of most of the 7-hydroxycoumarin derivatives was low in liver cytosol of human and pig, whereas it was high with most compounds in dog and intermediate in rat, mouse, rabbit, and sheep. Sulfonation of the 7-hydroxycoumarin derivatives followed Michaelis-Menten kinetics with K-m values of 0.1-12 mu M, V-max of 0.005-1.7 mu mol/(min * g protein) and intrinsic clearance (V-max/K-m) of 0.004-1.9 L/(min * g cytosolic protein). Fluorescence based measurement of sulfonation of 7-hydroxycoumarin derivatives provides a sensitive and convenient high-throughput assay to determine sulfonation rate in different species and tissues and can be applied to evaluate sulfonation kinetics and inhibition.
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