Silver diamine fluoride, a caries restorative agent, induces cytotoxicity in primary human gingival fibroblasts

Silver diamine fluoride (SDF) is commonly used in clinical settings to manage dental caries in young children. A major drawback of SDF is its tendency to darken carious lesions, turning them brown or black, which has drawn criticism. This study investigates the cytotoxic effects of SDF on human gingival fibroblasts (hGF).hGF cells were exposed to varying concentrations of SDF (0.0001%, 0.001%, and 0.005%) for a 24-hour period. We analysed cytotoxicity, the potential for reactive oxygen species (ROS) production, mitochondrial function, morphological indicators of apoptosis, and key molecular markers of apoptosis.The findings revealed that SDF exposure led to significant, dose-dependent cytotoxicity and ROS generation in hGF. Morphological changes consistent with apoptosis were observed. Furthermore, SDF disrupted the balance of Bax and Bcl-2 proteins and reduced the expression of proliferating cell nuclear antigen in these cells. In animal studies, single SDF application for 3 h resulted in mild structural alterations of gingival tissue and basilar hyperplasia in rats.Overall, the findings demonstrate that SDF exhibits cytotoxicity towards hGF, primarily through intracellular ROS production and subsequent apoptosis. Additionally, the <i>in vivo</i> experiments validate the mild toxic effects of SDF on rat gingival tissues. Developing controlled drug delivery approaches could help mitigate SDF's toxicity in clinical applications.