scholarly journals Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts

2019 ◽  
Vol 33 ◽  
pp. 205873841982774 ◽  
Author(s):  
Dorina Lauritano ◽  
Marcella Martinelli ◽  
Alessandro Baj ◽  
Giada Beltramini ◽  
Valentina Candotto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Gingival Tissue ◽  
Gingival Fibroblast ◽  
Gingival Hyperplasia ◽  
Gingival Fibroblasts ◽  
Drug Induced ◽  
Gingival Overgrowth

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 ( CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts.

scholarly journals Molecular Aspects of Drug-Induced Gingival Overgrowth: An In Vitro Study on Amlodipine and Gingival Fibroblasts

2019 ◽  
Vol 20 (8) ◽  
pp. 2047 ◽  
Author(s):  
Dorina Lauritano ◽  
Alberta Lucchese ◽  
Dario Di Stasio ◽  
Fedora Della Vella ◽  
Francesca Cura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
In Vitro Study ◽  
Gingival Fibroblast ◽  
Gingival Hyperplasia ◽  
Drug Induced ◽  
Gingival Overgrowth ◽  
Molecular Aspects ◽  
Gene Expression Levels

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.

scholarly journals Morpho-functional effects of different universal dental adhesives on human gingival fibroblasts: an in vitro study

Odontology ◽  
2020 ◽  
Author(s):  
Stefano Pagano ◽  
Guido Lombardo ◽  
Egidia Costanzi ◽  
Stefania Balloni ◽  
Stefano Bruscoli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Morphological Changes ◽  
Cell Damage ◽  
Human Gingival Fibroblasts ◽  
Gingival Tissue ◽  
Type I ◽  
Gingival Fibroblasts ◽  
Depth Analysis ◽  
Universal Adhesives

AbstractTo analyze the effects of four universal adhesives (Optibond Solo Plus—OB, Universal Bond—UB, Prime&Bond Active—PBA, FuturaBond M + —FB) on human gingival fibroblasts in terms of cytotoxicity, morphology and function. After in vitro exposure for up to 48 h, fibroblast viability was determined by the MTT assay determined, morphology by phase-contrast microscopy and migration by the scratch wound assay. Expression levels of IL1β, IL6, IL8, IL10, TNFα and VEGF genes were assessed by RT-PCR and their protein production by Western blot analysis. Apoptosis and cell cycle were analyzed by flow cytometry. OB and UB induced early morphological changes on fibroblasts (3 h) with extended cell death at 24 h/48 h. Gene expression of collagen type I and fibronectin increased fivefold compared with controls, elastin disappeared and elastase increased threefold, indicating gingival tissue tended to become fibrotic. Only UB and OB increased gene expression of inflammatory markers: IL1β at 3 and 48 h (up to about three times), IL6 and IL8 at 3 h (up to almost four times) which corresponded to the increase of the activated form NF-kB. All adhesives showed an effect on the functionality of fibroblasts with cytotoxic effect time and concentration dependent. Among all the OB and UB adhesives, they showed the greatest cell damage. The in-depth analysis of the effects of universal adhesives and possible functional effects represents an important information for the clinician towards choosing the most suitable adhesive system.

Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts

2015 ◽  
Vol 34 (11) ◽  
pp. 1073-1082 ◽  
Author(s):  
SS Soydan ◽  
K Araz ◽  
FV Senel ◽  
E Yurtcu ◽  
F Helvacioglu ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Mtt Assay ◽  
In Vitro Study ◽  
Osteonecrosis Of The Jaw ◽  
Human Gingival Fibroblasts ◽  
Gingival Tissue ◽  
Proliferation Index ◽  
Gingival Fibroblasts ◽  
Inhibition Of Proliferation

Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate ( n = 240), PAM ( n = 240), and control groups ( n = 60). Based on the MTT assay results, 10−4, 10−5, 10−6, and 10−7 M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10−4–10−5 M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time ( p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher ( p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.

scholarly journals Mechanism of Drug-induced Gingival Overgrowth: Phenytoin Inhibits the Apoptosis of Human Gingival Fibroblasts

2021 ◽  
Vol 20 (2) ◽  
pp. 109-116
Author(s):  
Reiri Takeuchi ◽  
Hiroko Matsumoto ◽  
Chieko Taguchi ◽  
Yuichiro Okada ◽  
Masaru Mizuta ◽  
...  
Keyword(s):  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Drug Induced ◽  
Gingival Overgrowth

Phenytoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin do not Alter the Effects of Bacterial and Amplified Plaque Extracts on Cultures of Fibroblasts from Normal and Overgrown Gingivae

1987 ◽  
Vol 66 (8) ◽  
pp. 1393-1398 ◽  
Author(s):  
Q.T. Smith ◽  
J.E. Hinrichs
Keyword(s):  
Cell Strain ◽  
Gingival Tissue ◽  
Gingival Fibroblast ◽  
Gingival Fibroblasts ◽  
Gingival Overgrowth ◽  
Cell Numbers ◽  
Wide Range ◽  
A Cell ◽  
Cell Strains ◽  
Interaction Between Drugs

Local irritation of gingival tissue by plaque is among the factors which affect development of gingival overgrowth in patients undergoing chronic phenytoin (PHT) therapy. Variability in the cytotoxicity of plaque components or of plaque substances plus PHT and/or its metabolites toward gingival fibroblasts may relate to whether gingival overgrowth forms in a particular patient. Fibroblasts from healthy and overgrown gingivae were incubated with (a) PHT and its major human metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), (b) microbial and "amplified" plaque extracts, and (c) microbial and "amplified" plaque extracts plus PHT and HPPH. Cell numbers and cell-associated protein were determined for each incubation preparation. A wide range in cytotoxic response to a particular microbial or plaque extract occurred among cell strains. Plaque extracts from different subjects had variable cytotoxicity toward a cell strain. The differences among fibroblast strains in response to an extract and the variability in cytotoxicity of different plaque extracts toward a cell strain were not related to their source from normal or overgrown gingivae. Cell numbers and cell-associated protein were similar for incubation mixtures containing extracts with and without PHT and HPPH. These data do not show differences among cytotoxicity levels of plaque extracts, the response of particular gingival fibroblast strains to plaque components, or interaction between drugs and certain plaque samples which explain development of gingival overgrowth in some subjects receiving chronic PHT therapy.

scholarly journals Cytokine Responses to Treponema pectinovorum andTreponema denticola in Human Gingival Fibroblasts

2000 ◽  
Vol 68 (9) ◽  
pp. 5284-5292 ◽  
Author(s):  
Connie S. Nixon ◽  
Michelle J. Steffen ◽  
Jeffrey L. Ebersole
Keyword(s):  
Cell Lines ◽  
Cell Cultures ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Fibroblast Cell ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblast ◽  
Gingival Fibroblasts ◽  
Cytokine Profiles ◽  
Fibroblast Cell Lines

ABSTRACT Human gingival fibroblasts were challenged with Treponema pectinovorum and Treponema denticola to test three specific hypotheses: (i) these treponemes induce different cytokine profiles from the fibroblasts, (ii) differences in cytokine profiles are observed after challenge with live versus killed treponemes, and (iii) differences in cytokine profiles are noted from different gingival fibroblast cell lines when challenged with these treponemes. Three normal gingival fibroblast cell cultures were challenged withT. pectinovorum and T. denticola strains, and the supernatants were analyzed for cytokine production (i.e., interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, IL-10, gamma interferon, macrophage chemotactic protein 1 [MCP-1], platelet-derived growth factor, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor). Unstimulated fibroblast cell lines produced IL-6, IL-8, and MCP-1. T. pectinovorum routinely elicited the greatest production of these cytokines from the fibroblast cell lines, increasing 10- to 50-fold over basal production. While T. denticola also induced IL-6 and IL-8 production, these levels were generally lower than those elicited by challenge with T. pectinovorum. MCP-1 levels were significantly lower after T. denticola challenge, and the kinetics suggested that this microorganism actually inhibited basal production by the fibroblasts. No basal or stimulated production of the other cytokines was observed. Significant differences were noted in the responsiveness of the various cell lines with respect to the two species of treponemes and the individual cytokines produced. Finally, dead T. pectinovorum generally induced a twofold-greater level of IL-6 and IL-8 than the live bacteria. These results supported the idea that different species of oral treponemes can elicit proinflammatory cytokine production by gingival cells and that this stimulation did not require live microorganisms. Importantly, a unique difference was noted in the ability of T. pectinovorum to induce a robust MCP-1 production, while T. denticolaappeared to inhibit this activity of the fibroblasts. While the general cytokine profiles of the fibroblast cell cultures were similar, significant differences were noted in the quantity of individual cytokines produced, which could relate to individual patient variation in local inflammatory responses in the periodontium.

scholarly journals Cyclosporin A and Phenytoin Modulate Inflammatory Responses

2009 ◽  
Vol 88 (12) ◽  
pp. 1131-1136 ◽  
Author(s):  
A.M.M. Suzuki ◽  
A. Yoshimura ◽  
Y. Ozaki ◽  
T. Kaneko ◽  
Y. Hara
Keyword(s):  
Cyclosporin A ◽  
Inflammatory Responses ◽  
Chinese Hamster ◽  
Human Gingival Fibroblasts ◽  
Common Side Effect ◽  
Gingival Fibroblasts ◽  
Toll Like Receptor ◽  
Gingival Overgrowth ◽  
Anti Epileptic Drug ◽  
Tlr4 Ligand

Gingival overgrowth is a common side-effect of administration of the immunosuppressant cyclosporin A and the anti-epileptic drug phenytoin. While cyclosporin-induced gingival overgrowth is often accompanied by gingival inflammation, phenytoin-induced gingival overgrowth usually forms fibrotic lesions. To determine whether these drugs alter the inflammatory responses of gingival fibroblasts, we investigated the effects of cyclosporin and phenytoin on Toll-like receptor (TLR)-mediated responses to microbial components. In Chinese hamster ovary reporter cell lines, cyclosporin alone triggered signaling, whereas phenytoin down-regulated signaling induced by the TLR2 or TLR4 ligand. In human gingival fibroblasts, cyclosporin alone did not induce evident inflammatory responses, but augmented the expression of CD54 and the production of interleukin (IL)-6 and IL-8 induced by TLR ligands, whereas phenytoin attenuated those responses. Cyclosporin also augmented CD54 expression in gingiva of mice injected with lipopolysaccharide. These results indicated that cyclosporin positively and phenytoin negatively modulated inflammatory responses of human gingival fibroblasts.

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