The UDP glucuronosyltranferase UGT2B17 en zyme is the main steroid glucuronidation enzyme of the UGT isotopes with more than double the glucuronida tion activity compared to the second most active enzyme involved in glucuronidation of testosterone, UGT2A1. The metabolism of testosterone by UGT2B17 has been shown to differ between individuals selleck kinase inhibitor owing to the varia tions in the expression of UGT2B17, which has been found to alter with ethnicity, affecting the excreted ster oid concentrations. In in vitro studies, the rate of testosterone glucuronidation has also been shown to be reduced with inhibitors of UGT2B17, such as non ster oidal anti inflammatory drugs. Whilst various drugs and compounds are glucuronidated as a substrate and inhibit UGT2B17, little is known about the inhibi tory effects common dietary substances could have on UGT2B17 and testosterone glucuronidation.

Recently, green and white teas and purified catechin constituents have been shown to inhibit the key testos terone glucuronidation enzyme UGT2B17 in a supersome based assay. Red wine is another rich source of phenolic compounds that have been found to exert anti oxidant health benefits in humans. Given the inhibitory effects of green and white tea on UGT2B17, along with the debate on red wine and pros tate cancer, it is timely to investigate if phenolic com pounds in red wine have an inhibitory effect on testosterone metabolism and excretion. The aim of this study was to analyze the inhibitory effects of a dietary red wine sample and the common phenolic compounds found in red wine, independent of the effects of alcohol, on the glucuronidation of testos terone through the inhibition of UGT2B17.

A further aim was to study the potential inhibitory effect of the common wine by product 4 ethylphenol on testosterone glucuronidation. Materials and methods Materials Testosterone, acetonitrile, ethanol, gallic Carfilzomib acid, chlorogenic acid, caffeic acid and quercetin were purchased from Sigma Aldrich. Dimethyl sulfoxide, methanol and high performance liquid chromatography grade water were purchased from Fisher Scientific. The UGT2B17 enzymes where purchased as human UGT2B17 supersomes from BD Biosciences. UDPGA was purchased as a UGT reaction solution from BD Biosciences. The MgCl2 and Tris HCl buffers, along with alamethicin were purchased together as a UGT reac tion mixture from BD Biosciences. The red wine sample used was a Cabernet Syrah red wine pur chased from a local supermarket. All solvents used where HPLC grade. Methods For general screening, HPLC analysis of testosterone glucuronidation was conducted on an Agilent 1260 HPLC system using an Ascentis Supelco C18 column, 25 cm x 406 mm i. d, 5 uM at 25 C column temperature.