Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.242
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
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Surgical removal remains the first-line treatment for CRC; however, nonsurgical options remain important tools for treatment. Currently, treatments such as 5-fluorouracil (5-FU), a widely administered chemotherapeutic agent utilized in the treatment of CRC, presents known beneficial effects, but also significant side effects. Hydrogen-rich water (HRW) has demonstrated beneficial effects in numerous species, including humans, in many disease models, including various cancers. One attractive aspect of HRW is the high safety profile and low rates of side effects combined with its promising therapeutic effects.
New treatments with potential positive effects in CRC are desperately needed, particularly treatments with high safety profiles and low side effects. HRW may fit the criteria as a safe potential treatment for CRC, either as a stand-alone treatment or in combination with conventional treatments.
We aimed to evaluate the efficacy of HRW on a CRC model compared to 5-FU and control, as well as the combination treatment of HRW and 5-FU compared to 5-FU alone, HRW alone, or control. We measured tumor size, tumor weight, fibrosis, and collagen content, as well as oxidative stress (OS) and antioxidant activity (AA) in mice with induced CRC. These objectives allow us to determine the therapeutic efficacy and mechanistic insight of HRW with or without 5-FU, as well as determine if there are additive benefits in a combinational treatment to guide future clinical studies.
Six- to eight-week-old female inbred Balb/c mice were injected with 5 × 105 CT-26 cells (100 μL) into the left rear flank (day 0). When tumor volumes reached 80-100 mm3, 24 mice bearing tumors were randomly divided into four groups. Mice were either left untreated (control) or treated with 5-FU (intraperitoneal injection, 5 mg/kg every other day), high-concentration HRW produced by magnesium tablets (ad libitum in drinking water, as well as by oral gavage 200 μL daily), or both HRW and 5-FU.
We report that molecular hydrogen dissolved in water (HRW) was as effective as 5-FU, with more preferential outcomes relating to higher AA and lower OS. Importantly, the combination of HRW and 5-FU was superior to either therapy on its own, presenting the possibility that HRW may be explored as an adjuvant therapy alongside conventional chemotherapeutics.
HRW may be a novel safe adjuvant therapy for treating CRC, either as a stand-alone therapy, or preferably, alongside conventional chemotherapeutics.
Clinical research to evaluate the effects of HRW as a treatment for CRC, both alone and in combination with 5-FU and other chemotherapeutics, is highly warranted.