Rapid Human Skin Barrier Disruption by Sodium Dodecyl Sulfate and Associated Molecular Mechanisms

BACKGROUND: Epithelial barrier disruption is a hallmark of allergic skin diseases. Sodium dodecyl sulfate (SDS), a surfactant in household cleaning products, is known to impair the barrier. METHODS: We used a physiologically relevant ex vivo human skin combined with real-time electrical impedance spectroscopy (EIS) to monitor barrier integrity after SDS exposure. Multi-omics analyses, including RNA sequencing and proximity extension-based proteomics, characterized molecular responses. Barrier permeability and oxidative stress were evaluated in primary keratinocytes, and the protective effects of N-acetylcysteine (NAC) and nicotinamide (NAM) were assessed in both air-liquid interface keratinocyte cultures and ex vivo skins. RESULTS: Even a 1-min SDS exposure caused a rapid EIS decline, indicating immediate barrier compromise. 5-min exposures produced dose-dependent EIS decline with broad suppression of barrier and immune mediators (e.g., CXCL11, MCP4, and HNMT), 6-h exposure sustained skin barrier loss and associated inflammatory and remodeling programs. Proteomic signatures highlighted AREG, JUN, and ITGA6 can track skin damage, while CST5 and PRDX1 correlated with the preservation. Transcriptomics corroborated these changes, showing up-regulation of stress and repair programs-endoplasmic reticulum stress, oxidative stress, sphingolipid biosynthesis, and epidermal differentiation pathways. NAC/NAM reduced SDS-induced reactive oxygen species, cytotoxicity, and permeability in primary keratinocytes, and restored EIS values in ex vivo skin. CONCLUSION: Short-term SDS exposure rapidly disrupts human skin barrier integrity through oxidative stress-driven suppression of structural/immune mediators and activation of stress/remodeling pathways. NAC and NAM effectively mitigated damages, highlighting antioxidants as preventive interventions for surfactant-induced skin barrier dysfunction.