Abstract
The epicatechin (EC) thio derivatives 4β-(S-cysteinyl)-epicatechin (Cys-EC) and 4β-(S-cysteaminyl)-epicatechin (Cya-EC) are compounds that may provide protection from oxidation via mechanisms involving either the flavonoid moiety or the nonphenolic cysteine or cysteamine part of the molecule. Because the metabolically modified molecules may be the actual active species, we estimated the absorption/metabolization of the thio derivatives through the small intestine in vitro and studied the body distribution of the compounds and their metabolites in rats. The analysis of the samples generated was done using a high-performance liquid chromatograph coupled to a UV detector and a tandem mass spectrometer. We show that Cya-EC follows the same phase II metabolization pattern as EC, whereas Cys-EC is transported with the intact catechol moiety through the small intestine and effectively metabolized systemically. We also found that Cya-EC generates Cys-EC in vivo, which provides evidence for a Cya-EC-mediated cytoprotective effect through cysteamine/cystine exchange with subsequent cysteine transport, ubiquitously throughout the organism.
Footnotes
This work was supported by the Spanish Ministry of Science and Technology [Awards PPQ2000-0688-C05-03, PTR1995-0611-OP].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.035279.
↵
The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
-
ABBREVIATIONS:
- Cys-EC
- 4β-(S-cysteinyl)-epicatechin
- EC
- (−)-epicatechin
- Cya-EC
- 4β-(2-aminoethylthio)-epicatechin or 4β-(S-cysteaminyl)-epicatechin
- HPLC
- high-performance liquid chromatography
- MS
- mass spectrometry
- TFA
- trifluoroacetic acid
- COMT
- catechol O-methyl transferase
- SAM
- S-adenosyl-l-methionine
- MS/MS
- tandem mass spectrometry
- AU
- arbitrary units
- FS
- full-scan
- MRM
- multiple reaction monitoring
- MES
- 4-morpholineethanesulfonic acid
- DTT
- dithiothreitol
- Me
- methyl
- Gluc
- glucuronidyl
- UDPGA
- uridine diphosphate glucuronic acid.
- Received July 6, 2010.
- Accepted September 3, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|