Effects of Lithium Chloride and Boric Acid on Cell Viability, Wound Healing, and Oxidative Stress Response in HaCaT Cells and Spheroids

Objective: This study aimed to investigate the effects of lithium chloride (LiCl) and boric acid (BA), administered alone or in combination, on viability, wound healing, spheroid morphology, and oxidative stress-related parameters in Human Adult low Calcium high Temperature keratinocyte cell line (HaCaT) models.

Methods: HaCaT spheroids were treated with different concentrations of LiCl and BA, either alone or in combination, and viability was evaluated at 24, 48, and 72 hours. Spheroid morphology was assessed by diameter and area measurements. Cell migration was analyzed using an in vitro scratch assay. Oxidative stress-related responses were determined by measuring advanced oxidation protein products (AOPP), total sulfhydryl groups (TSH), and malondialdehyde (MDA). Statistical comparisons were performed against the control group.

Results: Lithium chloride induced an early reduction in HaCaT spheroid viability, particularly at 24 hours, whereas this effect was not sustained at later time points. Boric acid alone tended to preserve viability, and its combination with 10 mM LiCl showed a more favorable viability profile than combinations containing 20 mM LiCl. Morphometric analysis demonstrated that 10 mM LiCl increased spheroid diameter and area at 48 hours, while BA co-treatment attenuated this effect. Scratch assay findings revealed treatment-related differences in wound closure, indicating altered keratinocyte migratory behavior. Among the biochemical parameters, the most evident changes were observed in AOPP, whereas TSH showed limited variation, and MDA remained relatively stable.

Conclusion: Lithium chloride and BA exerted distinct and context-dependent effects in HaCaT cell and spheroid models. Boric acid showed supportive and modulatory effects on viability, spheroid morphology, and wound healing under selected conditions. These findings suggest that LiCl and BA differentially influence keratinocyte responses and oxidative stress-related processes.

Cite this article as: Dümür S, Biltekin B, Uzun H. Effects of lithium chloride and boric acid on viability, wound healing, and oxidative stress responses in human adult low calcium high temperature keratinocyte cell line cells and spheroids. Cerrahpasa Med J. 2026, 50, 0054, doi: 10.5152/cjm.2026.26054.