2022 · Li — Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway
Super-Abstract
Applying hydrogen-rich saline directly to skin wounds in mice accelerated wound closure and reduced inflammation compared to regular saline, with the Nrf-2/HO-1 antioxidant pathway identified as the key mechanism. Additional cell-culture experiments confirmed that hydrogen-rich medium reduces oxidative stress in human epidermal cells. This is an animal and cell study; results cannot be directly transferred to humans. (Oxidative Medicine and Cellular Longevity, 2022.)
Commentary
Wound healing is routinely delayed by excessive reactive oxygen species (ROS) generated at injury sites, driving chronic inflammation and cell death. Hydrogen gas is known to selectively neutralize hydroxyl radicals (·OH) and peroxynitrite — two particularly damaging ROS — without interfering with beneficial signaling ROS. This study tests local (topical) hydrogen-rich saline (HRS) in a mouse wound model rather than systemic administration, which is an important distinction. Wound closure time, histology, inflammatory cytokines (pro-inflammatory markers were reduced), and the apoptosis index were all improved by HRS treatment. The mechanistic insight centers on Nrf-2 (nuclear factor erythroid 2-related factor 2), a master regulator of antioxidant gene expression, and its downstream target HO-1 (heme oxygenase-1). HRS application upregulated Nrf-2 and HO-1, providing a coherent molecular explanation. The human cell line used (HaCaT — immortalized non-tumorigenic keratinocytes) supports mechanistic plausibility but is not the same as a wound in a living human.
Key quotes
- „local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation.“ — primary functional outcome in the mouse wound model
- „hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway.“ — the proposed antioxidant mechanism in cell culture
- „This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.“ — authors' outlook — explicitly framed as preclinical
Our assessment
A well-designed animal and in-vitro study with a plausible mechanistic pathway (Nrf-2/HO-1). Local hydrogen application is a less-studied delivery route compared to inhalation or drinking, making this methodologically interesting. However, all results are preclinical: mice and cultured human cells are not substitutes for controlled human wound-healing trials. The effect size and optimal dosing for humans remain unknown.
Study design
- Type: animal study (in-vivo) + cell culture (in-vitro) · Model: Kunming mice wound model (4 groups: control, saline, HRS local, HRS intraperitoneal) + HaCaT human epidermal cells · H₂ delivery: local topical application of hydrogen-rich saline (HRS) to wound surface
- Result: HRS local treatment shortened wound closure, reduced pro-inflammatory cytokines and lipid peroxidation, decreased apoptosis index, upregulated Nrf-2 expression; mechanism confirmed via Nrf-2/HO-1 pathway activation in HaCaT cells
Abstract
Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this study, Kunming (KM) mice were used to set up a wound model. All the mice were randomly divided into the control, the local treatment with saline group, the local treatment with the hydrogen-rich saline group, and the intraperitoneal injection of the hydrogen-rich saline group. To evaluate the impact of hydrogen-rich saline on wound healing, we assessed the wound healing rate, wound closure time, histomorphology, oxidative stress indicators, inflammatory cytokines, the apoptosis index, and the expression of the nuclear factor-erythroid-related factor 2(Nrf-2). Furthermore, the immortalized nontumorigenic human epidermal (HaCaT) cells were chosen to investigate the therapeutic effects of hydrogen-rich medium on oxidative stress and its underlying mechanisms. The results showed that local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation. Meanwhile, it decreased the cell apoptosis index and increased the Nrf-2 expression. Besides, hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway. In conclusion, local treatment of hydrogen-rich saline exhibits the healing-promoting function through antioxidant, anti-inflammatory, and antiapoptotic effects. Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.
Source & links
Screenshot of the PubMed page
This page mirrors the published abstract (© the authors / publisher) for reference and citation. The canonical source is the PubMed record linked above. This is not medical advice.