Glucoraphasatin and glucoraphenin, a redox pair of glucosinolates of brassicaceae, differently affect metabolizing enzymes in rats.

Brassica vegetables are an important dietary source of glucosinolates (GLs), whose breakdown products exhibit anticancer activity. The protective properties of Brassicaceae are believed to be due to the inhibition of Phase-I or induction of Phase-II xenobiotic metabolizing enzymes (XMEs), thus enhancing carcinogen clearance. To study whether GLs affect XMEs and the role of their chemical structure, we focused on two alkylthio GLs differing in the oxidation degree of the side chain sulfur. Male Sprague-Dawley rats were supplemented (per oral somministration by gavage) with either glucoraphasatin (4-methylthio-3-butenyl GL; GRH) or glucoraphenin (4-methylsulfinyl-3-butenyl GL; GRE), at 24 or 120 mg/kg body weight in a single or repeated fashion (daily for four consecutive days), and hepatic microsomes were prepared for XME analyses. Both GLs were able to induce XMEs, showing different induction profiles. While the inductive effect was stronger after multiple administration of the higher GRH dosage, the single lower GRE dose was the most effective in boosting cytochrome P-450 (CYP)-associated monooxygenases and the postoxidative metabolism. CYP3A1/2 were the most affected isoforms by GRH treatment, whereas GRE induced mainly CYP1A2 supported oxidase. Glutathione S-transferase increased up to approximately 3.2-fold after a single (lower) GRE dose and UDP-glucuronosyl transferase up to approximately 2-fold after four consecutive (higher) GRH doses. In conclusion, the induction profile of these GLs we found is not in line with the chemopreventive hypothesis. Furthermore, the oxidation degree of the side chain sulfur of GLs seems to exert a crucial role on XME modulation.