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Skin-derived volatile organic compounds trigger redox signalling pathways in human keratinocytes via gas-phase interaction

Finnegan, Melissa, Bolikava, V., Walsh, N. and Morrin, A. (2025) Skin-derived volatile organic compounds trigger redox signalling pathways in human keratinocytes via gas-phase interaction. RSC Advances, 39 . ISSN 2046-2069

Abstract
Human skin emits a diverse range of volatile organic compounds (VOCs) originating from both endogenous metabolic activity and microbial transformation of sweat and sebum. While these volatiles have been profiled extensively, their potential to influence host cellular processes remains largely unexplored. In this study, we investigate the capacity of five skin-relevant VOCs—nonanal, decanal, 6-methyl-5-hepten2-one (6MHO), acetic acid (AA), and 2-ethyl-1-hexanol (2EH) – to induce redox signalling pathways in keratinocytes. We demonstrate that selected compounds, particularly nonanal, decanal and AA, induce intracellular reactive oxygen species (ROS) and activate the Nrf2–Keap1 antioxidant defence mechanism. Using both conventional liquid-phase treatment and a custom-designed headspace system for gasphase treatment, we show that these VOCs elicit this signalling response from both liquid and gas phases. These findings provide the first mechanistic evidence that endogenous or microbially-derived VOCs from skin can function as gaseous redox modulators, capable of triggering protective cellular responses from a distance. This work presents new evidence for cell–cell volatile communication in skin and through its resident microbiota, offering insights into the signalling potential of volatile metabolites.
Metadata
Item Type:Article (Published)
Refereed:Yes
Subjects:Physical Sciences > Analytical chemistry
Physical Sciences > Chemistry
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health
DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Publisher:Royal Society of Chemistry
Official URL:https://pubs.rsc.org/en/content/articlelanding/202...
Copyright Information:Authors
ID Code:31582
Deposited On:29 Sep 2025 11:08 by Gordon Kennedy . Last Modified 29 Sep 2025 11:08
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