| Rank |
Pathway / Axis |
Cancer / Tumor Context |
Normal Tissue Context |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
Selective ROS/RNS buffering (•OH, ONOO− emphasis) |
Oxidative damage tone ↓ (context-dependent) |
Radiation/chemo oxidative injury ↓ |
P, R |
Rapid cytoprotection |
Landmark work proposes H2 selectively reduces highly reactive species (e.g., hydroxyl radical) rather than globally suppressing signaling ROS. Treat as "selective antioxidant" rather than broad ROS quencher. |
| 2 |
Nrf2 antioxidant response (Keap1/Nrf2; SOD/GPx/GSH systems) |
Stress adaptation modulation (context-dependent) |
Nrf2 ↑; endogenous antioxidant enzymes ↑ |
R, G |
Endogenous antioxidant upshift |
Multiple reviews describe H2 as engaging Nrf2-linked programs and increasing antioxidant enzyme activity; direction in tumors is model-specific and should not be oversold as uniformly anti-tumor. |
| 3 |
NF-κB inflammatory transcription |
Inflammatory/pro-survival transcription ↓ (context) |
Inflammation ↓ (tissue protective) |
R, G |
Anti-inflammatory signaling |
Commonly reported downstream of redox modulation: reduced NF-κB activity and reduced inflammatory cytokine outputs. |
| 4 |
NLRP3 inflammasome (priming/activation) |
Inflammasome signaling ↓ (context) |
NLRP3 activation ↓; tissue injury signaling ↓ |
R, G |
Inflammasome dampening |
Often described as part of an antioxidant–anti-inflammatory synergy (Nrf2↑ with NF-κB/NLRP3↓). Use "reported" language. |
| 5 |
Mitochondrial protection / mitochondrial ROS |
Mito-stress tone ↓ (context) |
Mitochondrial function preserved; oxidative injury ↓ |
R, G |
Bioenergetic stabilization |
Frequently reported as reduced mitochondrial oxidative injury and improved cellular resilience in injury/inflammation models. |
| 6 |
Radiation/CCRT toxicity mitigation (clinical relevance) |
Adjunct use: may reduce acute radiation toxicities without obvious loss of tumor control (early evidence) |
Mucositis/dermatitis/inflammation severity ↓ (reported) |
G |
Supportive care |
Clinical studies report feasibility/safety and reduced radiotherapy-related toxicities in selected settings; treat as supportive/adjunct, not standalone anti-cancer therapy. |
| 7 |
Apoptosis / proliferation control |
Mixed reports: apoptosis ↑ or neutral depending on model |
Often anti-apoptotic in injury models |
G |
Context-dependent cell fate shift |
Unlike classic cytotoxins, H2 effects on apoptosis/proliferation are not uniform; keep as model-dependent and secondary. |
| 8 |
Clinical safety signal (inhalation studies) |
— |
Generally well tolerated at low concentrations in studied settings |
— |
Translation constraint / safety framing |
Human safety studies exist for low-concentration inhalation; practical use must be medical-grade and safety-controlled due to flammability risk. |