Diş Hekimliği Fakültesi / Faculty of Dentistry

Permanent URI for this collectionhttps://hdl.handle.net/11727/2120

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    Effects of Alendronate and Pamidronate on Apoptosis and Cell Proliferation in Cultured Primary Human Gingival Fibroblasts
    (2015) Soydan, S. S.; Araz, K.; Senel, F. V.; Yurtcu, E.; Helvacioglu, F.; Dagdeviren, A.; Tekindal, M. A.; Sahin, F.; 0000-0002-6026-0045; 0000-0001-8990-8282; 0000-0001-7308-9673; 0000-0003-4930-8164; 0000-0002-4060-7048; 0000-0002-4475-0861; 25636638; AAH-8887-2021; P-2877-2014; AAC-7232-2020; AAA-2998-2021; AES-7155-2022; U-9270-2018
    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.
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    The Effects of Ozone Application on Genotoxic Damage and Wound Healing in Bisphosphonate-Applied Human Gingival Fibroblast Cells
    (2018) Akdeniz, Sidika Sinem; Beyler, E.; Korkmaz, Y.; Yurtcu, E.; Ates, U.; Araz, K.; Sahin, F. I.; Torun, O. Y.; 0000-0003-4930-8164; 0000-0001-7308-9673; 28699091; AAA-2998-2021; HGA-3970-2022; AAC-7232-2020
    Medication-related osteonecrosis of the jaws (MRONJ) is an extremely therapy-resistant disease involving the jaws especially following bisphosphonate treatment. Bisphosphonates accumulate in bone in concentrations sufficient to be directly toxic to the oral epithelium. Current therapeutic options are inadequate for the prevention and treatment of MRONJ. The aim of this study was to investigate effects of ozone gas plasma therapy on wound healing in bisphosphonate-applied human fibroblasts. Human primary gingival fibroblasts were cultured. Cytotoxic concentrations (IC50) of bisphosphonates (pamidronate (PAM), alendronate (ALN), and zoledronate (ZOL)) were determined by MTT test. A 60 mu g/mu l for 30 s of ozone gas plasma application was performed to all experimental culture flasks after drug treatment at 24-h intervals as 3 s/cm(2). Genotoxic damages were evaluated by comet assay and wound healing was determined by in vitro scratch assay. PAM, ALN, and ZOL applications caused genotoxic damage on primary human gingival fibroblast DNA. Ozone gas plasma therapy significantly decreased the genotoxic damage (p < 0.05), and this application provided 25, 29, and 27% less genotoxic damage in order of ALN, PAM, and ZOL groups. Ozone gas plasma therapy significantly increased wound healing rates both in postsurgical 24th and 48th hours for all doses of experimental drug groups (p < 0.05). The ozone gas plasma application decreased genotoxic damage effect of bisphosphonate usage while improved the wound closure rate on human gingival fibroblasts. Ozone gas plasma therapy may be helpful in prevention of gingival healing delay in MRONJ pathogenesis especially when applied simultaneously with surgical intervention.