Intake of Molecular Hydrogen in Drinking Water Increases Membrane Transporters, p-Glycoprotein, and Multidrug resistance-associated Protein 2 without Affecting Xenobiotic-metabolizing Enzymes in Rat Liver

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 4 weeks. 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, 4A), glutathione-S-transferase and UDP-glucuronosyltransferase. Except for a slight 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. 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 the expression of p-glycoprotein and Mrp2 protein.

Combating Oxidative Stress and Inflammation in COVID‐19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives

“…However, H 2 can increase GSH levels [96] by activating the Nrf2 pathway [97]. A nonsignificant increase in GSH, GSH/GSSG, and GSH peroxidase combined with a decrease in GSSG levels in rat livers fed with hydrogen-rich water compared to control was reported [98]. Interestingly, both endogenous and exogenous oxidants have been shown to need hours to significantly affect GSH levels in the majority of cells [88].…”

“…Inhibits the over-expression of inflammatory factors (IL-6, IL-8 and TNF-α) [98] Downregulates the expression of proapoptotic Fas proteins Up-regulates the expression of the anti-apoptotic protein Bcl2…”

“…Attenuates septic shock-induced organ injury [98] Decreases neutrophil infiltrate in the alveoli 8 Oxidative Medicine and Cellular Longevity revealed that small changes in the cellular redox status may alter signaling pathways, and the GSH/GSSG ratio can serve as a good indicator of the cellular redox state. While the increase in the GSH/GSSG leads to proliferation, the decrease in the GSH/GSSG causes apoptosis.…”

“…Protects the intestinal mucosa from mechanical injury [98] Reduces the pathological changes of the small intestine Inhibits bacterial translocation Protects the function of other organs in the body 9 Oxidative Medicine and Cellular Longevity sword because, on the one hand, the redox status stays in the range of homeostasis despite a significant amount of oxidative stress. On the other hand, by the time the GSH/GSSG ratio has changed enough to be detected, it may be too late and/or too difficult to reestablish homeostasis by pharmacological interventions.…”