Hydrogen peroxide pathway in ulcerative colitis: Promises and challenges in translating novel pathogenesis to clinical practice

Table 1 Comparison of pathological mechanisms and treatment methods between the new hypothesis and traditional theories of ulcerative colitis

Mechanism	H2O2 hypothesis	Traditional treatment
Root cause	Excessive H2O2 production and accumulation in colonic epithelial cells	Abnormal activation or dysregulation of the immune system[17]
Initial event	Mitochondrial H2O2 generation increased - intracellular accumulation - transmembrane diffusion	Aberrant T-cell activation - cytokine release[18]
Neutrophil recruitment	Direct chemotactic effect of H2O2	IL-8, CXCL1, and other chemokine-mediated recruitment[19]
Inflammatory cascade	H2O2 - neutrophil infiltration - tissue damage - additional H2O2 release	Th1/Th17 activation - TNF-α/IL-17 increased - inflammatory amplification[20]
Tissue damage mechanism	H2O2-mediated disruption of tight junction proteins - epithelial barrier dysfunction	Cytotoxic T cells and NK cell-mediated epithelial cell killing[21]
Primary drugs	STS, R-DHLA	Mesalazine, biologics, immunosuppressants, JAK inhibitors[22]
Drug action	H2O2 neutralization (extracellular and intracellular)	Anti-inflammatory, immunosuppression

CXCL1: Chemokine CXC ligand 1; H₂O₂: Hydrogen peroxide; IL: Interleukin; JAK: Janus kinase; LPS: Lipopolysaccharide; NK: Natural killer; R-DHLA: R-Dihydrolipoic acid; STS: Sodium thiosulfate; TNF: Tumor necrosis factor.