Regulation of microRNAs by molecular hydrogen contributes to the prevention of radiation-induced damage in the rat myocardium

Abstract

microRNAs (miRNAs) constitute a large class of post-transcriptional regulators of gene expression. It has been estimated that miRNAs regulate up to 30% of the protein-coding genes in humans. They are implicated in many physiological and pathological processes, including those involved in radiation-induced heart damage. Biomedical studies indicate that molecular hydrogen has potential as a radioprotective agent due to its antioxidant, anti-inflammatory, and signal-modulating effects. However, the impact of molecular hydrogen on the expression of miRNAs in the heart after irradiation has not been investigated. This study aimed to explore the involvement of miRNA-1, -15b, and -21 in the protective action of molecular hydrogen on rat myocardium damaged by irradiation. The results showed that the levels of malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) increased in the rat myocardium after irradiation. Treatment with molecular hydrogen- rich water (HRW) reduced these values to the level of non-irradiated controls. miRNA-1 is known to be involved in cardiac hypertrophy, and was significantly decreased in the rat myocardium after irradiation. Application of HRW attenuated this decrease in all evaluated time periods. miRNA-15b is considered to be anti-fibrotic, anti-hypertrophic, and anti-oxidative. Irradiation downregulated miRNA-15b, whereas administration of HRW restored these values. miRNA-21 is connected with cardiac fibrosis. We observed significant increase in miRNA-21 expression in the irradiated rat hearts. Molecular hydrogen lowered myocardial miRNA-21 levels after irradiation. This study revealed for the first time that the protective effects of molecular hydrogen on irradiation-induced heart damage may be mediated by regulating miRNA-1, -15b, and -21.

Study details

Article type

Original Research

Disease / injury model

Radiation-induced heart disease (RIHD) in rats

Duration

45 days

Outcome

Positive

Findings

Molecular hydrogen-rich water (HRW) administered to rats prevented or reversed radiation-induced increases in oxidative stress (MDA), inflammation (TNF-α), and dysregulation of key cardiac microRNAs (miRNA-1, -15b, -21), suggesting a protective effect against radiation-induced heart damage via modulation of these markers.