Effect of the beta-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases.

The Journal of Pharmacy and Pharmacology
Lauren Oleson, Michael H Court

Abstract

Glucuronidation studies using microsomes and recombinant uridine diphosphoglucuronosyltransferases (UGTs) can be complicated by the presence of endogenous beta-glucuronidases, leading to underestimation of glucuronide formation rates. Saccharolactone is the most frequently used beta-glucuronidase inhibitor, although it is not clear whether this reagent should be added routinely to glucuronidation incubations. Here we have determined the effect of saccharolactone on eight different UGT probe activities using pooled human liver microsomes (pHLMs) and recombinant UGTs (rUGTs). Despite the use of buffered incubation solutions, it was necessary to adjust the pH of saccharolactone solutions to avoid effects (enhancement or inhibition) of lowered pH on UGT activity. Saccharolactone at concentrations ranging from 1 to 20 mM did not enhance any of the glucuronidation activities evaluated that could be considered consistent with inhibition of beta-glucuronidase. However, for most activities, higher saccharolactone concentrations resulted in a modest degree of inhibition. The greatest inhibitory effect was observed for glucuronidation of 5-hydroxytryptamine and estradiol by pHLMs, with a 35% decrease at 20 mM saccharolactone concentration...Continue Reading

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Citations

Feb 14, 2012·The Journal of Pharmacology and Experimental Therapeutics·Amanda LoGuidiceUrs A Boelsterli
Jan 8, 2014·Expert Opinion on Drug Metabolism & Toxicology·Li Di
Nov 4, 2015·Bioorganic & Medicinal Chemistry·Muhammad TahaKhalid Mohammed Khan
Jun 13, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hua SunBaojian Wu
Feb 22, 2017·Molecular Nutrition & Food Research·Rungnapa BoonpawaIvonne M C M Rietjens
Jun 7, 2017·British Journal of Pharmacology·Rungnapa BoonpawaIvonne M C M Rietjens
Feb 3, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Helinä KahmaJanne T Backman
Feb 23, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chunying GaoQingcheng Mao
Apr 26, 2014·British Journal of Sports Medicine·Tiia KuuranneNorbert Baume
May 17, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lian Yee Yip, Eric Chun Yong Chan
Feb 24, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert L WalskyTheunis C Goosen
Sep 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brandon T GuffordMary F Paine
Jun 29, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yusuke MasuoHiroshi Suzuki
Oct 10, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael A Zientek, Kuresh Youdim
Oct 24, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nenad ManevskiKarine Litherland
Oct 11, 2014·Rapid Communications in Mass Spectrometry : RCM·Jeongmin JooKwang-Hyeon Liu
Mar 19, 2021·Planta medica·Yue BaiJie Hou

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