{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:35:34Z","timestamp":1766716534005,"version":"3.48.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["01-773\/1"],"award-info":[{"award-number":["01-773\/1"]}]},{"name":"the Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-137\/2025-03\/200111"],"award-info":[{"award-number":["451-03-137\/2025-03\/200111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Amlodipine, a widely prescribed calcium channel blocker, has been associated with gingival enlargement, yet the mechanisms underlying this adverse effect remain unclear. The present study aimed to explore molecular and histopathological factors potentially contributing to gingival changes in patients receiving amlodipine therapy, with a particular focus on molecules implicated in extracellular matrix turnover and tissue remodeling. Methods: The study included three groups of participants: patients with amlodipine-induced gingival enlargement, patients with gingival enlargement of inflammatory origin, and amlodipine-treated patients without gingival overgrowth. Gingival tissue samples were analyzed using hematoxylin-eosin staining to assess inflammatory changes and general tissue architecture, and Picrosirius Red staining to visualize collagen fibers. Relative gene expression of alpha-smooth muscle actin (\u03b1-SMA), IL-13, MMP-1, and procollagen was determined by real-time PCR, while collagen content was quantified using ImageJ software. Results: Histopathological evaluation revealed a less pronounced inflammatory response in amlodipine-related gingival enlargement compared to those who did not use amlodipine. The highest expression of \u03b1-SMA was detected in patients who did not receive amlodipine, whereas IL-13 and procollagen expression were markedly elevated in the amlodipine-induced group compared to others. MMP-1 expression was significantly lower in amlodipine-treated patients relative to those who did not use amlodipine, suggesting impaired collagen degradation. These findings, together with our previous results indicating enhanced expression of profibrotic mediators, suggest that altered extracellular matrix metabolism is potentially dominant in this condition. Conclusions: Amlodipine-induced gingival enlargement appears to involve a multifactorial process characterized by a prominent fibrotic component, reduced matrix degradation, and secondary inflammation.<\/jats:p>","DOI":"10.3390\/ph19010045","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T16:41:19Z","timestamp":1766594479000},"page":"45","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histopathological and Molecular Characterization of Amlodipine-Induced Gingival Enlargement: Insights into Fibrotic Mechanisms"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-735X","authenticated-orcid":false,"given":"Jana","family":"Mojsilovi\u0107","sequence":"first","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Kosti\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-1709","authenticated-orcid":false,"given":"Sanja","family":"Vujovi\u0107 Risti\u0107","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-4566","authenticated-orcid":false,"given":"Momir","family":"Stevanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milovan","family":"Stevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-8157","authenticated-orcid":false,"given":"Sanja","family":"Kne\u017eevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-8380","authenticated-orcid":false,"given":"Nemanja","family":"Jovi\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","first-page":"613","article-title":"Oral manifestations of commonly prescribed drugs","volume":"102","author":"Glick","year":"2020","journal-title":"Am. 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