Protective Effects of Sulforaphane and Kojic Acid Against Arsenic-Induced Inflammatory and Apoptotic Toxicity in HaCaT Cells

Background: Arsenic is an environmental toxicant associated with skin injury, inflammation, and apoptosis-related cellular responses. Human keratinocyte (HaCaT) cells are widely used to investigate the mechanisms of arsenic-induced skin toxicity and potential protective interventions. Sulforaphane and kojic acid have been reported to possess cytoprotective and anti-inflammatory properties in various experimental models. Aim: To evaluate the protective effects of sulforaphane and kojic acid against arsenic-induced cytotoxicity and alterations in inflammation- and apoptosis-related gene expression in HaCaT cells. Methods: HaCaT cells were exposed to arsenic (5 μM) alone or in combination with sulforaphane (5, 10, and 20 μM) or kojic acid (50, 100, and 200 μM). Cell viability was assessed using the MTT assay. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), BCL-2-associated X protein (BAX), and B-cell lymphoma 2 (BCL-2) were evaluated by quantitative real-time polymerase chain reaction (qPCR). Results: Arsenic exposure significantly reduced cell viability and increased TNF-α, IL-6, and BAX expression while decreasing BCL-2 expression. Treatment with sulforaphane or kojic acid improved cell viability and attenuated arsenic-induced changes in gene expression. Both compounds reduced TNF-α, IL-6, and BAX expression and partially restored BCL-2 expression compared with the arsenic-treated group. Sulforaphane generally produced a more consistent protective effect than kojic acid across the evaluated inflammatory and apoptosis-related markers. Conclusion: Arsenic induced cytotoxicity and significant transcriptional alterations associated with inflammatory and apoptosis-related responses in HaCaT cells. Sulforaphane and kojic acid mitigated these effects, with sulforaphane showing a more consistent protective profile. These findings suggest that both compounds may help attenuate arsenic-induced keratinocyte injury and provide a basis for further mechanistic investigation.