Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX 2 , iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1β and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1–2) ( p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1–1) ( p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity ( p < 0.001), MDA levels ( p < 0.001) and NFκB NLS P50 ( p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS ( p < 0.05), NFκB P65 ( p < 0.05), and negative immunoreaction to MMP-2 ( p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline ( p < 0.05). Immunofluorescence revealed decreased levels of P-selectin ( p < 0.001) after treatment with gliclazide 10 mg/kg ( p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.

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Curcumin, contained at Turmeric (Curcuma longa), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1β and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultravioletvisible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1β (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.