**Hsien-Tsung Yao \*, Yu-Hsuan Yang and Mei-Ling Li**

Department of Nutrition, China Medical University, 91 Hsueh-shih Road, Taichung 404, Taiwan **\*** Correspondence: htyao@mail.cmu.edu.tw; Tel.: +886-4-22053366 (ext. 7526); Fax: +886-4-22062891

Academic Editor: Ping-Chung Kuo Received: 26 June 2019; Accepted: 17 July 2019; Published: 19 July 2019

**Abstract:**Molecular hydrogen (H2) has been shown to have antioxidant and anti-inflammatory activities that may reduce the development and progression of many diseases. In this study, hydrogen-rich water (HRW) was obtained by reacting hybrid magnesium–carbon hydrogen storage materials with water. Then, the effects of intake of HRW on the activities of xenobiotic-metabolizing enzymes, membrane transporters, and oxidative stress in rats were investigated. Rats were given HRW ad libitum for four weeks. The results showed that intake of HRW had no significant effect on the activities of various cytochrome P450 (CYP) enzymes (CYP1A1, 1A2, 2B, 2C, 2D, 2E1, 3A, and 4A), glutathione-*S*-transferase, and Uridine 5- -diphospho (UDP)-glucuronosyltransferase. Except for a mild lower plasma glucose concentration, intake of HRW had no effect on other plasma biochemical parameters in rats. *p*-Glycoprotein and multidrug resistance-associated protein (Mrp) 2 protein expressions in liver were elevated after intake of HRW. However, HRW had no significant effects on glutathione, glutathione peroxidase, or lipid peroxidation in liver. The results from this study suggest that consumption of HRW may not affect xenobiotic metabolism or oxidative stress in liver. However, intake of HRW may increase the efflux of xenobiotics or toxic substances from the liver into bile by enhancing *p*-glycoprotein and Mrp2 protein expressions.

**Keywords:** molecular hydrogen; hydrogen-rich water; xenobiotic-metabolizing enzymes; membrane transporters; liver; oxidative stress
