The effect of Tumor Necrosis Factor alpha inhibitor on wound healing of oral mucosa in induced diabetic rats

*Department of oral diagnosis, college of dentistry, Hawler Medical University, Erbil, Iraq. **Ministry of health, Erbil, Iraq. Introduction Type 1 diabetes mellitus is a common chronic autoimmune disease, induced by permanent destruction of β pancreatic cells, and characterized by defects in insulin secretion and hyperglycemia. Long-term manifestations of diabetes include ret inopathy, neuropathy, nephropathy, defect in blood vessels, periodontitis, and other complications, such as impaired wound-healing. The delayed wound healing in diabetes is caused by complex factors such as reduced keratinocyte proliferation, diminished fibroblast migration and differentiation, and higher rate of apoptosis. Several of these defects have been linked to greater inflammation and proinflammatory cytokine production. In normal inflammation, necrotic tissues are removed to create a healthy environment for the growth of new tissue. In a pathological circumstances, such as that of diabetics, sluggish removal of necrotic tissue delays the onset of healing and results in chronic inflammation.A large number of growth factors are important in stimulating and orginizing cellular events that occur during normal wound healing. Among them, cytokines and chemokines are especially noted because of their roles in promoting inflammation, budding new blood vessels, leukocyte migration, and reepithelialization. Proinflammatory cytokines that are Background and objective: Impaired wound healing is a major complication of diabetes mellitus. This study was carried out to determine the healing process of oral mucosa in diabetic rats and the role of systemic tumor necrosis factor alpha inhibitor (infliximab). Methods: Thirty eight male rats were divided into two groups, the normoglycemic group (11 rats), and diabetic group (27 rats) that were rendered diabetic by alloxan injection. Two months later, wound was created in the lateral side of the tongue for both groups. The diabetic group was then subdivided into two subgroups, 14 rats received 5mg/kg infliximab subcutaneous injection at the day of wound creation while the other 13 rats received saline injection. After 7 days, biopsies of the tongue were collected and subjected to histological and histochemical procedure. Results: Histological examinations showed delayed healing in the diabetic group with persistence of epithelial discontinuity, large amount of granulation tissue and destruction of the underlying muscle fibers. In the subgroup injected with infliximab, reepitheliazation of the wound was demonstrated with well arranged underlying collagen fibers. Using PAS stain, diabetic group revealed a dramatically high amount of PAS positive precipitants in the lamina properia, especially in the wall of the blood vessels, while with infliximab injection, the PAS+ve precipitants were more prominent than normoglycemic group but less than diabetic group without infliximab. Conclusion: These findings suggest that infliximab accelerated mucosal wound healing in the diabetic rats with the formation of well organized connective tissue.