A1 Journal article (refereed)
In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species (2020)

Juvonen, R. O., Pentikäinen, O., Huuskonen, J., Timonen, J., Kärkkäinen, O., Heikkinen, A., Fashe, M., & Raunio, H. (2020). In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species. Xenobiotica, 50(8), 885-893. https://doi.org/10.1080/00498254.2020.1711544

JYU authors or editors

Publication details

All authors or editors: Juvonen, Risto O.; Pentikäinen, Olli; Huuskonen, Juhani; Timonen, Juri; Kärkkäinen, Olli; Heikkinen, Aki; Fashe, Muluneh; Raunio, Hannu

Journal or series: Xenobiotica

ISSN: 0049-8254

eISSN: 1366-5928

Publication year: 2020

Volume: 50

Issue number: 8

Pages range: 885-893

Publisher: Taylor & Francis

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1080/00498254.2020.1711544

Publication open access: Not open

Publication channel open access:

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/74580


1. Sulfonation is an important high affinity elimination pathway for phenolic compounds.

2. 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.

3. 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 Km values of 0.1–12 µM, Vmax of 0.005–1.7 µmol/(min * g protein) and intrinsic clearance (Vmax/Km) of 0.004–1.9 L/(min * g cytosolic protein).

4. 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.

Keywords: medicinal substances; coumarins; pharmacokinetics; liver; human beings; animals

Free keywords: sulfonation; liver; human; animal; 7-hydroxycoumarin

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2020

JUFO rating: 1

Last updated on 2022-20-09 at 14:17