Human and Experimental Toxicology, cilt.45, 2026 (SCI-Expanded, Scopus)
Introduction: Heated tobacco products (HTPs) are increasingly used among young people and adolescents, while their long-term toxicological effects remain insufficiently characterized. In parallel, frequent use of electronic devices has led to prolonged exposure to blue light (BL), a visible radiation that penetrates deeply into the skin and may exert phototoxic effects. Although the individual impact of these exposures has been studied, their combined effects on human skin are poorly understood. Methods: In this study, we investigated the dual toxicity of HTP-derived total particulate matter (TPM) and BL irradiation (4.32 and 17.28 J/cm2, respectively) in HaCaT human keratinocyte cell line. Cell viability via MTT test, intracellular reactive oxygen species (ROS), inflammatory markers, and matrix remodeling factors via ELISA, and autophagosome formation via western blotting were assessed following single and combined exposures. Results: Our findings demonstrated that BL and TPM co-exposure significantly reduced cell viability in a time-dependent manner and augmented intracellular ROS production. Co-exposure also up-regulated MMP-1 and IL-6 levels while increasing LC3β-II expression in human keratinocytes, suggesting the implication of oxidative stress, inflammatory signaling, and autophagy in the observed dual cytotoxicity. Discussion: These findings indicate that concurrent exposure to BL and HTPs may exacerbate epidermal damage beyond the effects of each stressor alone. The results highlight potential health concerns associated with modern lifestyle habits, particularly regarding skin toxicity, and support the need for further toxicological evaluation of combined environmental exposures.