Induced oral mucositis in Wistar rats treated with different drugs: Preventive potential in cytokine production

The aim of the present study was to investigate the preventive potential of pentoxifylline, atorvastatin and trans-caryophyllene in oral mucositis through histopathological analysis of wounds in the oral mucosa of Wistar rats treated with 5-FU, and to evaluate the immunomodulatory effect of these drugs on serum nitrite production, in situ IFN-gamma, TNF-alpha and TGF-beta, and TNF-alpha in tissues. A total of 32 male Wistar rats with an average age of 9 weeks and an average body weight of 250 g were divided into four treatment groups: Saline, trans-caryophyllene, pentoxifylline and atorvastatin. Oral mucositis was then induced. On days 3 and 4, the mucosa of the mouth of eight pre-treated animals in each group was bilaterally scarified twice with the tip of a sterile needle, with an anesthetic solution. Mucosal samples from animals treated with trans-caryophyllene preserved a thin epithelial lining associated with focal perivascular inflammatory infiltrates. Pentoxifylline-treated animals exhibited total epithelial loss in oral wounds with severe inflammatory infiltrates and mild re-epithelialization associated with mild and diffuse inflammatory infiltrates. Samples from atorvastatin-treated animals exhibited no epithelial dissolution, with preserved thin lining and mild diffuse inflammatory infiltrates. The analysis of TNF-alpha expression revealed improved results in trans-caryophyllene animals. The analysis of TGF-beta expression revealed positive mononuclear cells. Preventive treatment with atorvastatin was demonstrated to modulate the serum expression levels of TNF-alpha during all stages of the experiment. Treatment with trans-caryophyllene modulated serum IFN-gamma levels negatively, whereas treatment with atorvastatin and trans-caryophyllene maintained lower levels of IFN-gamma compared with the control group.