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Objective: To assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DESIGN: Wistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily., Results: The 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01)., Conclusion: Naltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Wound healing of oral traumatic ulcers (OTU) is strongly associated with cytokines and inflammatory cells, and the reduction of anti-inflammatory cells, such as lymphocyte B, may interfere with OTU repair. We aimed to evaluate the role of CD20 + cells in the healing process of OTU in rats., Design: Wistar male rats were divided into four groups: a control group (treated with 0.1 mL/kg of saline) and three groups treated with anti-CD20 rituximab (RTX) at 2.5, 10, or 40 mg/kg 24 h before OTU production. The animals were weighed (day 0) and euthanized on days 3, 7, 14, and 21 after ulceration. With Blood cells (hematological analysis) and the traumatically induced ulcers were clinically measured. The mucosal samples were histologically (scores 0-4), histochemically (collagen assay (picrosirius)), histomorphometrically (cell counting), and immunohistochemically (CD20 + , Tumor Necrosis Factor alpha(TNF-α), Interleukin(IL)- 1β, IL-6 and α-smooth-muscle-actin (α-SMA)) analyzed. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05)., Results: RTX leads to leukopenia, lymphocytopenia, and neutropenia (p < 0.001), and high doses reduced the OTU area (p = 0.001), impaired histologic scores (p < 0.05), and delayed polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, and total (p = 0.011), type-I (p = 0.008), and type-III (p = 0.021) collagen., Conclusion: RTX treatment reduced CD20 + cells in OTU (p = 0.001), TNF-α (p = 0.006), and α-SMA (p = 0.022) immunostaining and delayed IL-6 reduction (p = 0.006), with no influence in IL-1β immunostaining. CD20 + cell blockage by RTX reduced cell migration, acute inflammation, and wound healing in OTU., Competing Interests: Declaration of Competing Interest The authors present no conflicts of interest to declare. This work was partially financed by the Cearense Research Support Foundation (FUNCAP) in the form of a scientific initiation scholarship and had no intervention in the design and execution of this research., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to compare alveolar healing after tooth extraction in two experimental rat models using continuous or discontinuous dosing of sodium alendronate (ALN)., Design: Forty-eight male Wistar rats were divided into eight experimental groups (n = 6/group) and administered ALN (2.5, 5.0, or 7.5 mg/kg) by gavage, weekly, either intermittently or following a continuous regimen (2.5, 5.0, or 7.5 mg/kg) before tooth extraction. The positive control rats were administered zoledronic acid (ZA; 0.2 mg/kg, intravenous), whereas negative control rats received sterile saline (0.9% NaCl, gavage)., Results: Only the ZA-treated animals showed a larger radiolucent extraction site area compared to the saline group (p = 0.007). Small areas of bone tissue filling the alveoli were visualized in the 7.5 mg/kg continuous ALN group and compared with the saline group (p < 0.001). Increased amounts of empty osteocyte lacunae (p < 0.001) and osteoclasts with signs of apoptosis (p = 0.004) were observed in the continuous ALN groups (2.5, 5.0, and 7.5 mg/kg) compared with the saline group. Increased immunolabeling for TNF-α was observed in the 7.5 mg/kg discontinuous ALN group and all continuous ALN groups compared with the saline group (p < 0.001). The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was higher in the two continuous ALN groups (5.0 and 7.5 mg/kg) than in the saline group (p < 0.001)., Conclusions: Continuous administration of ALN impaired post-extraction alveolar bone healing in rats; however, discontinuation of ALN administration before tooth extraction allowed for adequate post-dental extraction alveolar healing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: TNF-α, which acts directly on osteoclastogenesis, may modify bone turnover. Thus, the objective of this study was to evaluate the influence of infliximab on extraction socket healing., Material and Methods: Eighty-four Wistar rats were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1 ml / kg) and submitted to lower first molar extraction protocol. The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The jaws were subjected to radiographic, histomorphometric, histochemical (picrosirius red) and immunohistochemical (TNF-α, RANKL and OPG) analysis., Results: No differences were observed between the groups in surgical difficulty parameters: mass of teeth, number of root fractures and surgical time. Lower area filling with bone as well as increased amounts of remaining cicatricial tissue were observed in the infliximab group at 14 days (p < 0.001). Lower scores for polymorphonuclear neutrophils were seen at 3 (p < 0.01) and 7 days (p < 0.001), lower mononuclear counts at 7 days (p < 0.01) and lower osteoclast counts at 7 and 14 days (p < 0.01 and p < 0.001, respectively). Additionally, reduced TNF-α, RANKL and OPG immunoreactivity were observed, especially at 7 days (p < 0.05)., Conclusion: TNF-α inhibitor may alter the bone repair capacity after tooth extraction, especially in the initial repair periods, by lower expression of TNF α, RANKL and OPG. Thus, additional caution may be needed in patients who use this class of medication after dental extraction., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats., Design: BRONJ was induced by zoledronic acid (ZA) infusion (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically., Results: The BRONJ groups showed a higher radiolucent area compared with the control groups (p<0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/kg groups had a greater number of bacterial colonies (p<0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p<0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy., Conclusion: Thus, DEX or NIM therapy was not effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA., (Copyright © 2017 Elsevier Ltd. All rights reserved.)