ENDOPLASMIC RETICULUM INVOLVEMENT IN DRUG-INDUCED GINGIVAL OVERGROWTH

Gingival overgrowth is an undesirable and well-recognized side effect following the use of various drugs, such as phenytoin, nifedipine and cyclosporine A (CsA). Apoptosis constitutes a necessary process for constant tissue remodelling, its absence playing a critical role in gingival overgrowth. The aim of this study was to evaluate the effects of THP (thapsigargin), brefeldin A, cyclopiazonic acid, and capsaicin on the endoplasmic reticulum (ER) and their involvement in apoptosis of normal fibroblasts compared with those treated with drugs. These substances are well known for inducing stress in the ER through different mechanisms, thus leading to the induction of apoptosis. In conclusion, ER stress induction in normal fibroblasts using cyclopiazonic acid, THP, brefeldin A and capsaicin had no significant effects on mitochondrial permeability transition pore opening. In the case of CsA or nifedipine pre-treatment, cyclopiazonic acid, capsaicin and THP decreased mitochondrial calcein, suggesting that the opening of mitochondrial permeability transition pore (MPTP) is due to ER stress. For the phenytoin pre-treatment case, only cyclopiazonic acid, and capsaicin have induced significant effects on MPTP.