Abstract
Enterolactone (EL) is a gut microbe metabolite of the flaxseed lignan secoisolariciresinol diglucoside (SDG). Studies suggest a correlation between EL systemic levels and protective effects against cancer and cardiovascular disease. EL's oral bioavailability is low and highly variable due to extensive first-pass metabolism. To better understand the contribution of liver and intestine to first-pass glucuronidation we conducted an in vitro enzyme kinetic analysis of EL glucuronidation in liver and intestinal microsomes from both human and rat. An intrinsic clearance (CLint) value was calculated using the substrate depletion approach. In addition to monitoring substrate depletion, HPLC analysis allowed detection of EL glucuronides which were further substantiated by LC-MS/MS. EL monoglucuronide was identified in human and rat liver and intestinal microsomes. Enzyme kinetic studies indicated the extent of hepatic microsomal glucuronidation exceeded intestinal glucuronidation in both human and rat, while the human liver CLint value was slightly higher than that of rat liver. The CLint value generated in human intestinal microsomes was only one third of human liver, whereas the CLint of rat jejunum or colon was one-twentieth of rat liver suggesting the human intestine makes a greater contribution to EL glucuronidation than rat intestine. Our results suggest that both liver and intestine contribute to EL glucuronidation and the human intestine may exert a greater influence on the first-pass glucuronidation of EL than rat intestine. The rat might underestimate the extent of intestinal metabolism of EL relative to human.
Keywords: Enterolactone, flaxseed, glucuronidation, intestine, liver, lignan.
The Natural Products Journal
Title:The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans
Volume: 3 Issue: 3
Author(s): Chaojie Lin, Ed S Krol and Jane Alcorn
Affiliation:
Keywords: Enterolactone, flaxseed, glucuronidation, intestine, liver, lignan.
Abstract: Enterolactone (EL) is a gut microbe metabolite of the flaxseed lignan secoisolariciresinol diglucoside (SDG). Studies suggest a correlation between EL systemic levels and protective effects against cancer and cardiovascular disease. EL's oral bioavailability is low and highly variable due to extensive first-pass metabolism. To better understand the contribution of liver and intestine to first-pass glucuronidation we conducted an in vitro enzyme kinetic analysis of EL glucuronidation in liver and intestinal microsomes from both human and rat. An intrinsic clearance (CLint) value was calculated using the substrate depletion approach. In addition to monitoring substrate depletion, HPLC analysis allowed detection of EL glucuronides which were further substantiated by LC-MS/MS. EL monoglucuronide was identified in human and rat liver and intestinal microsomes. Enzyme kinetic studies indicated the extent of hepatic microsomal glucuronidation exceeded intestinal glucuronidation in both human and rat, while the human liver CLint value was slightly higher than that of rat liver. The CLint value generated in human intestinal microsomes was only one third of human liver, whereas the CLint of rat jejunum or colon was one-twentieth of rat liver suggesting the human intestine makes a greater contribution to EL glucuronidation than rat intestine. Our results suggest that both liver and intestine contribute to EL glucuronidation and the human intestine may exert a greater influence on the first-pass glucuronidation of EL than rat intestine. The rat might underestimate the extent of intestinal metabolism of EL relative to human.
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Cite this article as:
Lin Chaojie, Krol S Ed and Alcorn Jane, The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans, The Natural Products Journal 2013; 3 (3) . https://dx.doi.org/10.2174/2210315511303030001
DOI https://dx.doi.org/10.2174/2210315511303030001 |
Print ISSN 2210-3155 |
Publisher Name Bentham Science Publisher |
Online ISSN 2210-3163 |
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