Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2017; 23(27): 4920-4934
Published online Jul 21, 2017. doi: 10.3748/wjg.v23.i27.4920
Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice
Ching-Pin Lin, Wen-Chen Chuang, Fung-Jou Lu, Chih-Yen Chen
Ching-Pin Lin, Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan
Ching-Pin Lin, Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Wen-Chen Chuang, Fung-Jou Lu, Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Chih-Yen Chen, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
Chih-Yen Chen, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 112, Taiwan
Author contributions: Lin CP and Chuang WC contributed equally to this work; Lin CP, Chuang WC, Lu FJ and Chen CY designed the research; Lin CP and Chuang WC performed the experiments and analyzed the data; Lu FJ contributed to the reagents, materials and analysis tools; Chen CY discussed the data and drafted the manuscript; Lin CP and Chuang WC wrote the manuscript.
Supported by a grant from the Chung Shan Medical University, No. CSMU0150011.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee, Chung-Shan Medical University (IACUC protocol number: 1745).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Chih-Yen Chen, MD, PhD, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Road Taipei 112, Taiwan.
Telephone: +886-2-28712121-3763 Fax: +886-2-28711058
Received: February 28, 2017
Peer-review started: March 2, 2017
First decision: March 16, 2017
Revised: March 31, 2017
Accepted: June 18, 2017
Article in press: June 19, 2017
Published online: July 21, 2017

To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice.


In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.


The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.


HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.

Keywords: Hydrogen, Chronic plus binge EtOH feeding, Antioxidant, Protective cytokine, Acyl ghrelin, Female mice

Core tip: Hydrogen-rich water (HRW), a safe and effective antioxidant with minimal side effects, is used in preventive and clinical applications. Few studies have investigated the effects of hydrogen on early alcoholic liver disease. The present study evaluated the potential protective effects of HRW against chronic ethanol (EtOH)-induced early liver injury and the underlying mechanisms in female mice after chronic-plus-binge EtOH feeding. HRW pretreatment protected against mild EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress tumor necrosis factor-alpha and interleukin (IL)-6 and induce IL-10 and IL-22, thereby activating antioxidant enzymes against oxidative stress. These results suggest that HRW helps prevent and treat EtOH-induced early liver injury.