ArticleClinical oral investigations2015
Nitric oxide-mediated cytotoxic effect induced by zoledronic acid treatment on human gingival fibroblasts.
Article in Clinical oral investigations, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Mitigating Effect and Mechanism of Polydeoxyribonucleotide Against Zoledronic Acid-Induced Growth Suppression of Human Gingival Fibroblasts.International journal of molecular sciences · 2025Article
- Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase.Bioengineered · 2021Article
- Choosing the Right Partner for Medication Related Osteonecrosis of the Jaw: What Central European Dentists Know.International journal of environmental research and public health · 2021Article
- Article
- The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes.Pharmaceuticals (Basel, Switzerland) · 2020Review
- VEGF/VEGF-R/RUNX2 Upregulation in Human Periodontal Ligament Stem Cells Seeded on Dual Acid Etched Titanium Disk.Materials (Basel, Switzerland) · 2020Article
- Enhanced VEGF/VEGF-R and RUNX2 Expression in Human Periodontal Ligament Stem Cells Cultured on Sandblasted/Etched Titanium Disk.Frontiers in cell and developmental biology · 2020Article
- A Novel Role of Ascorbic Acid in Anti-Inflammatory Pathway and ROS Generation in HEMA Treated Dental Pulp Stem Cells.Materials (Basel, Switzerland) · 2019Article
- Mechanical loading increases pro-inflammatory effects of nitrogen-containing bisphosphonate in human periodontal fibroblasts.Clinical oral investigations · 2018Article
- Article
- Reactive oxygen species are required for zoledronic acid-induced apoptosis in osteoclast precursors and mature osteoclast-like cells.Scientific reports · 2017Article
- Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy.Molecules (Basel, Switzerland) · 2016Article
- In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.Clinical oral investigations · 2016Article
- Dose-Dependent Effects of Zoledronic Acid on Human Periodontal Ligament Stem Cells: AnCell transplantationArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe aim of our work was to evaluate the role of nitric oxide (NO) in the in vitro response of human gingival fibroblasts (HGFs) to 1, 5, 10, and 100 μM doses of zoledronic acid (ZA), a bisphosphonate largely used in the clinical practice and for which several adverse effects are reported. MATERIALS AND
methodsPhase contrast microscopy and live/dead staining were used to evaluate HGFs morphology; cell viability, collagen type I and interleukin 6 (IL-6) secretion were evaluated by 3-[4,5-dimethyl-thiazol-2-yl-]-2,5-diphenyl tetrazolium bromide (MTT) and enzyme-linked immunosorbent assay (ELISA) assays. Reactive oxygen species (ROS) production and mitochondrial membrane potential were evaluated by flow cytometry; NO production and NOS activity by spectrophotometric analysis; endothelial NOS (eNOS) and neuronal NOS (nNOS) expression by immunofluorescence.
resultsViable fibroblasts are evidenced in control sample while floating dead cells and cells close to detachment phase in ZA-treated sample, in agreement with decreased level of collagen type I. Control sample shows higher number of viable cells respect to ZA-treated one and ROS production increases when ZA is added. Released NO in ZA-treated sample appears higher and NO overproduction is related to increased nNOS activity. IL-6 secretion level is higher in ZA-treated sample than in control one.
conclusionsOur results suggest ROS involvement in NO overproduction, due to nNOS recruitment, both at low and high doses. In turn, NO release seems to be able to trigger the inflammatory response only when high doses are administered, thus confirming the ZA cytotoxic effect on HGFs. CLINICAL RELEVANCE: The knowledge of ZA-mediated cytotoxicity mechanisms on HGFs allows to better understand drug pharmacological activity.
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