Veena K M, Mohammed Hasil V, Shenoy Prashanth, Abhijna Ballal R, Shetty Sanath Kumar
Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya Deemed to be a University, Deralakatte, Mangalore, Karnataka, 575018, India.
Yenepoya Technology Incubator, Yenepoya Dental College, Yenepoya Deemed to be a University, Deralakatte, Mangalore, Karnataka, 575018, India.
Mol Biotechnol. 2025 Mar 14. doi: 10.1007/s12033-025-01397-6.
Drug-induced gingival enlargement (DIGE) is an abnormal overgrowth that may occur as a side effect in some patients when calcium channel blockers, immunosuppressants, or anticonvulsants are taken. The prevalence of DIGE was shown to be 70% for phenytoin (30% for other anticonvulsant medicines) and 50-80% for cyclosporine. The usage of these medications is increasing as new indications emerge. These drugs act through a common mechanism of action at the cellular level by inhibiting intracellular calcium influx. DIGE is characterized by the presence of varied quantities of inflammatory infiltrates, primarily plasma cells, and an excessive build-up of extracellular matrix like-collagen. Fibroblasts, the cells responsible for collagen synthesis, may become hyperactive, leading to the excessive production of collagen fibers. This increased collagen content can result in the enlargement of gingival tissues. As collagen deposits increase, it hinders normal oral care routines, masticatory processes, and esthetics. In this study, we compared the cytotoxicity of phenytoin, gabapentin, and cyclosporine on gingival fibroblast cells using the methyl thiazolyl-tetrazolium assay to understand their effect on gingival fibroblast cells. Phenytoin had the greatest half-maximal inhibitory concentration (IC50) with a value of 305.78 µg/ml, followed by gabapentin with a value of 260.44 µg/ml and cyclosporin with a value of 243.79 µg/ml. Understanding the cytotoxic thresholds of these medications is essential for improving patient outcomes and minimizing the incidence of gingival enlargement in those requiring long-term therapy. According to the study, cytotoxicity increases along with medication concentration. These findings will assist medical professionals in selecting the drug that poses the least risk of adverse effects on gingival health, ultimately guiding more informed prescribing practices.
药物性牙龈增生（DIGE）是一种异常增生，在某些患者服用钙通道阻滞剂、免疫抑制剂或抗惊厥药时可能作为副作用出现。据显示，苯妥英钠导致DIGE的发生率为70%（其他抗惊厥药物为30%），环孢素为50 - 80%。随着新适应症的出现，这些药物的使用正在增加。这些药物通过在细胞水平上抑制细胞内钙内流的共同作用机制发挥作用。DIGE的特征是存在不同数量的炎症浸润，主要是浆细胞，以及细胞外基质如胶原蛋白的过度积聚。负责胶原蛋白合成的成纤维细胞可能会变得活跃过度，导致胶原蛋白纤维过度产生。这种增加的胶原蛋白含量会导致牙龈组织增生。随着胶原蛋白沉积增加，会妨碍正常的口腔护理程序、咀嚼过程和美观。在本研究中，我们使用甲基噻唑基四氮唑试验比较了苯妥英钠、加巴喷丁和环孢素对牙龈成纤维细胞的细胞毒性，以了解它们对牙龈成纤维细胞的影响。苯妥英钠的半数最大抑制浓度（IC50）最高，为305.78 µg/ml，其次是加巴喷丁，为260.44 µg/ml，环孢素为243.79 µg/ml。了解这些药物的细胞毒性阈值对于改善患者预后以及将长期治疗患者的牙龈增生发生率降至最低至关重要。根据该研究，细胞毒性随药物浓度增加而增加。这些发现将帮助医疗专业人员选择对牙龈健康产生不良反应风险最小的药物，最终指导更明智的处方实践。
