Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways

Abstract

Molecular hydrogen (H2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H2 on liver function. Rats exposed 2 h daily to H2 either by drinking HRW (H2 dissolved in H2O) or by breathing 4% H2 gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H2-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H2 induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.

Prospects of molecular hydrogen in cancer prevention and treatment

“…On the one hand, H 2 can inhibit the damage of cellular DNA by ·OH and ONOO– to prevent cancer development; on the other hand, H 2 can remove ROS from cancer cells and inhibit multiple ROS-dependent metabolic signaling pathways to suppress cancer development. Studies have confirmed that H 2 can effectively reduce oxidative stress caused by various pathological conditions, including cancers, and promote the restoration of redox homeostasis (Adzavon et al 2022 ; Shi et al 2016 ; Kawai et al 2012 ).…”

“…4 ). H 2 , on the other hand, combats oxidative stress in various disease conditions and restores redox balance in the body’s environment by regulating the NADH/NADPH pathway (Adzavon et al 2022 ; Tao et al 2019 ), thereby safeguarding T cell activation and preventing apoptosis. Moreover, in this condition, compared with routine anti-tumor medicine, the high permeability of H 2 grants it to easily penetrate inside the tumor, even into structures such as the mitochondria of the TILs.…”

Molecular Hydrogen: From Molecular Effects to Stem Cells Management and Tissue Regeneration

“…In studies performed on the model of aplastic anemia, it was shown that the use of H 2 influences mesenchymal stem cells, as it contributes to an increase in the number of colony-forming units [ 85 , 108 ]. In addition, the introduction of hydrogen positively modulates the state and functional activity of mitochondria in various cancer cells [ 109 ].…”

Mesenchymal Stem Cell Priming: Potential Benefits of Administration of Molecular Hydrogen

“…In addition, H 2 quickly penetrates several organelles, as well as the blood–brain barrier, and is non-toxic even at high concentrations. Moreover, it is used frequently to treat disorders linked to oxidative stress because of its ability to interfere with reactive oxygen species (ROS) in living systems [ 14 ]. On the other hand, some researchers note that H 2 decreases the delayed-onset muscle soreness after downhill running [ 14 ].…”

“…Moreover, it is used frequently to treat disorders linked to oxidative stress because of its ability to interfere with reactive oxygen species (ROS) in living systems [ 14 ]. On the other hand, some researchers note that H 2 decreases the delayed-onset muscle soreness after downhill running [ 14 ]. Some researchers have demonstrated that it improves the muscle function during exercise without having any negative impact on blood oxidative markers [ 15 ].…”