Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 242-252
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.242
Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model
Fereshteh Asgharzadeh, Alex Tarnava, Asma Mostafapour, Majid Khazaei, Tyler W LeBaron
Fereshteh Asgharzadeh, Majid Khazaei, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
Alex Tarnava, Drink HRW, New Westminster, BC V3j0b6 Canada
Asma Mostafapour, Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
Tyler W LeBaron, Centre of Experimental Medicine, Institute for Heart Research Slovak Academy of Sciences, Bratislava 984104, Slovakia
Tyler W LeBaron, Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT 84720, United States
Tyler W LeBaron, Biological Research, Molecular Hydrogen Institute, UT 84721, United States
Tyler W LeBaron, Department of Physical Science, Southern Utah University, UT 84720, United States
Author contributions: All authors were involved in design of experiment; Asgharzadeh F, Mostafapour A, and Khazaei M carried out the experiments and wrote the methods and results sections; Tarnava A and LeBaron TW wrote the background, discussion and conclusion; and all authors agree to final manuscript.
Supported by the HRW Natural Health Products Inc. (dba Drink HRW), as well as by a grant from Mashhad University of Medical Sciences.
Institutional review board statement: The Mashhad University of Medical Sciences Committee on Animal Ethics has approved all animal protocols used in this research.
Institutional animal care and use committee statement: The Mashhad University of Medical Sciences Committee on Animal Ethics has approved all animal protocols used in this research. Reference Number: 991229; Date: July 10, 2020.
Conflict-of-interest statement: Tarnava A is involved in commercial entities with interest in the marketing of hydrogen-rich water; LeBaron TW has received travel reimbursement, honoraria, and speaking and consultancy fees from various academic and commercial entities regarding molecular hydrogen. All other authors report no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tyler W LeBaron, BSc, MSc, Director, Instructor, Research Scientist, Centre of Experimental Medicine, Institute for Heart Research Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovak Republic, Bratislava 984104, Slovakia. lebaront@molecularhydrogeninstitute.com
Received: May 19, 2021
Peer-review started: May 19, 2021
First decision: June 16, 2021
Revised: June 30, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: January 15, 2022
Processing time: 236 Days and 1.7 Hours
Abstract
BACKGROUND

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the world. Tumor removal remains the preferred frontline treatment; however, effective non-surgical interventions remain a high priority. 5-fluorouracil (5-FU) is a widely used chemotherapy agent, and molecular hydrogen (H2) has been recognized for its antioxidant and anti-inflammatory effects, with research also suggesting its potential anti-tumor effects. Therefore, H2 dissolved in water [hydrogen-rich water (HRW)], with or without 5-FU, may present itself as a novel therapeutic for CRC.

AIM

To investigate the effects of HRW, with or without 5-FU, as a novel therapeutic for CRC.

METHODS

CRC was induced in the left flank of inbred Balb/c mice. A total of 24 mice bearing tumors were randomly divided into four groups (n = 6 per group) and treated as follows: (1) Control group; (2) 5-FU group that received intraperitoneal injection of 5-FU (5 mg/kg) every other day; (3) H2 group that received HRW, created and delivered via dissolving the H2-generating tablet in the animals’ drinking water, with 200 μL also delivered by oral gavage; and (4) The combination group, H2 (administered in same way as for group three) combined with 5-FU administered same way as group two.

RESULTS

Administration of HRW + 5-FU significantly improved tumor weight, tumor size, collagen content and fibrosis as compared to the CRC control group. Specifically, HRW attenuated oxidative stress (OS) and potentiated antioxidant activity (AA), whereas 5-FU treatment exacerbated OS and blunted AA. The combination of HRW + 5-FU significantly reduced tumor weight and size, as well as reduced collagen deposition and the degree of fibrosis, while further increasing OS and decreasing AA compared to administration of 5-FU alone.

CONCLUSION

Administration of HRW, with or without 5-FU, may serve as a therapeutic for treating CRC.

Keywords: Colorectal cancer; Molecular hydrogen; 5-fluorouracil; Oxidative stress; Antioxidants; Inflammation

Core Tip: Colorectal cancer is a leading cause of death and is often treated with the chemotherapy drug, 5-fluorouracil (5-FU), which has some unwanted side effects. Molecular hydrogen (H2 gas) has antioxidant, anti-inflammatory, and anti-cancer effects. H2 gas can be dissolved in water to make hydrogen-rich water (HRW). The effects of HRW, 5-FU and the combination of HRW and 5-FU in a colorectal-cancer mouse model were examined. HRW and 5-FU decreased tumor size and weight with the combination being the most effective. In contrast to 5-FU, HRW attenuated oxidative stress and improved antioxidant activity.