Endoplasmic Reticulum Involvement in Drug-Induced Gingival Overgrowth

Abstract

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. RezumatHipercreșterea gingivală reprezintă un efect secundar ce apare la administrarea mai multor substanțe medicamentoase, precum fenitoină, nifedipină și ciclosporină. Apoptoza constituie un proces indispensabil pentru remodelarea tisulară continuă, iar absența acesteia joacă un rol important în hipercreșterea gingivală. Scopul prezentului studiu a fost evaluarea efectelor thapsigargin (THP), brefeldin A, acidului ciclopiazonic și a capsaicinei asupra reticulului endoplasmic (RE) și implicarea în apoptoza fibroblastelor tratate cu substanțele menționate. În concluzie, inducerea stresului la nivelul RE în culturile de fibroblaste normale tratate cu THP, brefeldin A, acid ciclopiazonic și capsaicină nu a influențat semnificativ deschiderea porului de permeabilitate tranzitorie mitocondrială (MPTP). În cazul tratamentului prealabil cu ciclosporină A sau cu nifedipină, acidul ciclopiazonic, capsaicina și THP au determinat scăderea încărcării mitocondriale cu calceină, sugerând că deschiderea MPTP se datorează stresului RE. În cazul pre-tratamentului cu fenitoină, doar acidul ciclopiazonic și capsaicina au indus modificări semnificative asupra MPTP.

Comparative in Vitro and in Ovo Study of the Cytotoxic Profile of Nicotine From Electronic Cigarettes Versus Chewing Gum

“…Nonetheless, these changes were not as pronounced as those observed with electronic cigarette-derived nicotine (Figure 4). According to the results of the study, the cell morphology displayed changes similar to those observed in the present study, indicating that apoptosis is involved [38]. Another study evaluating the potential effects of nicotine on human embryonic stem cell (hESC) line H9 observed morphological changes that affected cardiogenic differentiation of hESCs [20].…”

“…Results from the study were similar to those obtained in the present study, indicating that nicotine inhibits cell viability dose-dependently. Furthermore, it was noted that Nic induces cell apoptosis, resulting in a reduction in anti-apoptotic gene expression and an increase in pro-apoptotic gene expression [38]. According to the study conducted by Basma and colleagues regarding the effects of nicotine from electronic cigarettes, it is shown that it has a strong cytotoxic effect on cardiomyocytes, increasing the production of reactive oxygen species and altering genes involved in cell proliferation and apoptosis [3].…”