Absorption and metabolization of cytoprotective epicatechin thio conjugates in rats.

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.