Abstract
Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0–4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1–2-way/Bonferroni, Kruskal–Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.
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10787_2022_1046_MOESM1_ESM.tif
Supplementary file 1. IL-8 immunostaining profile maturation of OTU during healing in rats treated with different doses of INF. Immunohistochemistry, DAB-hematoxylin staining; light microscopy; magnification = 400 X; black barr = 50 µm
10787_2022_1046_MOESM2_ESM.tif
Supplementary file 2. FGF immunostaining profile maturation of OTU during healing in rats treated with different doses of INF. Immunohistochemistry, DAB-hematoxylin staining; light microscopy; magnification = 400 X; black barr = 50 µm
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Freitas, M.O., Fonseca, A.P.R., de Aguiar, M.T. et al. Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats. Inflammopharmacol 30, 1781–1798 (2022). https://doi.org/10.1007/s10787-022-01046-3
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DOI: https://doi.org/10.1007/s10787-022-01046-3