Hydrogen to patients with colon cancerScientific Research

Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model

Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model<br/ ><br/ >Asgharzadeh F, Tarnava A, Mostafapour A, Khazaei M, LeBaron TW. Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model. World J Gastrointest Oncol 2022; 14(1): 242-252 [PMID: 35116114 DOI: 10.4251/wjgo.v14.i1.242]

Fereshteh Asgharzadeh, Alex Tarnava, Asma Mostafapour, Majid Khazaei, Tyler W LeBaron

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Tumor resection remains the first-line treatment of choice; however, effective non-surgical intervention remains a high priority. 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug, and molecular hydrogen (H2) is known for its antioxidant and anti-inflammatory effects, and studies have pointed to its potential antitumor effects. Therefore, H2 dissolved in water [hydrogen-rich water (HRW)] with or without 5-FU may act as a new therapeutic agent for CRC.

Aim

To investigate the effect of HRW (with or without 5-FU) as a novel therapeutic agent for CRC.

Methods

CRC was induced in the left flank of inbred Balb/c mice. 24 tumor mice were randomly divided into 4 groups (n=6 in each group), and the treatment methods were as follows: (1) control group; (2) 5-FU group, intraperitoneal injection of 5-FU (5 mg/kg) every other day; ( 3) H2 group, the tablet that produces H2 is dissolved in animal drinking water to produce HRW administration, the same gavage administration of 200 μl; (4) combined group H2 (administration mode is the same as group three) combined administration with 5-FU The same way as group two.

Results

Administration of HRW + 5-FU significantly improved tumor weight, tumor size, collagen content, and fibrosis compared with CRC controls. Specifically, HRW attenuated oxidative stress (OS) and enhanced antioxidant activity (AA), whereas 5-FU treatment exacerbated OS and attenuated AA. Compared with 5-FU alone, the combination of HRW + 5-FU significantly reduced tumor weight and size, and decreased collagen deposition and fibrosis grade, while further increasing OS and decreasing AA.

Conclusion

Administration of HRW, with or without 5-FU, can be used as a therapeutic agent for the treatment of CRC.

References

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1.  Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14:89-103.
2.   Colorectal cancer: Overview.
3.  Surveillance, Epidemiology, and End Results (SEER) Program.   (2021). Cancer Stat Facts: Colorectal Cancer.
4.  Benitez Majano S, Di Girolamo C, Rachet B, Maringe C, Guren MG, Glimelius B, Iversen LH, Schnell EA, Lundqvist K, Christensen J, Morris M, Coleman MP, Walters S. Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden: a population-based study. Lancet Oncol. 2019;20:74-87.
5.  Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3:330-338.
6.  Yang Q, Ji G, Pan R, Zhao Y, Yan P. Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Mol Clin Oncol. 2017;7:891-896.
7.  Kang KM, Kang YN, Choi IB, Gu Y, Kawamura T, Toyoda Y, Nakao A. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011;1:11.
8.  Hirano SI, Aoki Y, Li XK, Ichimaru N, Takahara S, Takefuji Y. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study. Med Gas Res. 2021;11:104-109.
9.  Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer. Science. 1975;190:152-154.
10.  Runtuwene J, Amitani H, Amitani M, Asakawa A, Cheng KC, Inui A. Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ. 2015;3:e859.
11.  Golovko D, Kedrin D, Yilmaz ÖH, Roper J. Colorectal cancer models for novel drug discovery. Expert Opin Drug Discov. 2015;10:1217-1229.
12.  Moradi-Marjaneh R, Hassanian SM, Rahmani F, Aghaee-Bakhtiari SH, Avan A, Khazaei M. Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer. Curr Pharm Des. 2018;24:4626-4638.
13.  Amerizadeh F, Rezaei N, Rahmani F, Hassanian SM, Moradi-Marjaneh R, Fiuji H, Boroumand N, Nosrati-Tirkani A, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Avan A. Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem. 2018;119:10250-10261.
14.  Binabaj MM, Asgharzadeh F, Avan A, Rahmani F, Soleimani A, Parizadeh MR, Ferns GA, Ryzhikov M, Khazaei M, Hassanian SM. EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation. J Cell Physiol. 2019;234:11654-11661.
15.  Madesh M, Balasubramanian KA. A microtiter plate assay for superoxide using MTT reduction method. Indian J Biochem Biophys. 1997;34:535-539.
16.  Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol. 2014;15:47.
17.  LeBaron TW, Kura B, Kalocayova B, Tribulova N, Slezak J. A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules. 2019;24.
18.  Ichihara M, Sobue S, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles. Med Gas Res. 2015;5:12.
19.  Nogueira JE, Passaglia P, Mota CMD, Santos BM, Batalhão ME, Carnio EC, Branco LGS. Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status. Free Radic Biol Med. 2018;129:186-19
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Asgharzadeh F, Tarnava A, Mostafapour A, Khazaei M, LeBaron TW. Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model. World J Gastrointest Oncol 2022; 14(1): 242-252