Comparison of hydrogen administration methods in the treatment of radiation-induced heart disease in rats

Can J Physiol Pharmacol. 2026 Jan 1:104:1-13. doi: 10.1139/cjpp-2025-0085.

Abstract

Ionizing radiation is a known risk factor for the occurrence and development of cardiovascular diseases, particularly in patients receiving thoracic radiotherapy. This exposure leads to oxidative stress and inflammation, which can damage cardiac tissue and vascular endothelium. Molecular hydrogen (H2) has been recognized for its therapeutic potential, including antioxidant effects. In this study, male Wistar rats were irradiated with a dose of 10 Gy (X-rays) in the chest area. Two and 9 days post-irradiation, significant increases in lactate dehydrogenase (LDH), catalase, glutathione peroxidase activity, malondialdehyde, superoxide, and tumor necrosis factor alpha levels were observed in the rat blood plasma or heart tissue. Administration of H2 either via drinking H2-rich water (min. 4 mg/L) or inhaling H2 in air (4%), effectively decreased oxidative stress, LDH, and inflammatory proteins to normal levels. H2 also normalized the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associating protein 1 (Nrf2/Keap1) pathway, an important antioxidative response regulator activated by irradiation. Based on these results, we can conclude that H2 administration through both routes mitigated heart damage caused by irradiation after 2 and 9 days. The mitigating effect exerted more pronounced trend with H2 gas inhalation, but further research is needed for statistically relevant data and mechanistic insights.

Keywords: cardiovascular diseases; inflammation; molecular hydrogen; oxidative stress; radiation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism
  • Heart Diseases* / drug therapy
  • Heart Diseases* / etiology
  • Heart Diseases* / metabolism
  • Hydrogen* / administration & dosage
  • Hydrogen* / pharmacology
  • Hydrogen* / therapeutic use
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Radiation Injuries* / drug therapy
  • Radiation Injuries* / metabolism
  • Radiation Injuries, Experimental* / drug therapy
  • Radiation Injuries, Experimental* / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Hydrogen
  • Antioxidants
  • NF-E2-Related Factor 2
  • Kelch-Like ECH-Associated Protein 1
  • L-Lactate Dehydrogenase