Protective effect of angiotensin II receptor blocker against oxidative stress and inflammation in an oral mucositis experimental model.

BACKGROUND: The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin II receptor antagonist, on oral mucositis (OM) experimental model. METHODS: Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg day 1 and 40 mg/kg day 2). Animals (n = 10/group) were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle 30 minutes before 5-FU injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of IL-1ß, TNF-α, IL-10, TGF-ß, macrophage migration inhibitory factor (MIF), SOD, MMP-2 and FGF-2. In addition, IL-1ß and TNF-α levels were evaluated by ELISA. Myeloperoxidase activity (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were investigated by spectroscopic UV/VIS analysis. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantify the expression of IL-1ß, TNF-α, NF-κBp65, MKP1 and ACE2. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 protein levels were analysed by Western blot. RESULTS: Treatment with 10 mg/kg Olme reduced ulceration, inflammatory cell infiltration, MPO activity, MDA levels, iNOS and ERK1/2 proteins levels, MIF expression and TNF-α and IL-1ß of levels and gene expression. These findings were associated with a significant increase in the immunostaining of IL-10, FGF-2 and TGF-ß. In addition, gene expression of IL-1ß, TNF-α, NF-κBp65 MKP1 and ACE2 was decreased. CONCLUSION: Olmesartan at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis.

AIM: To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis. MATERIALS & METHODS: Male albino Wistar rats were divided randomly into five groups of twenty-one rats each, and given the following treatments for 10 days: (1) no ligature + water, (2) ligature + water, (3) ligature + 50 mg/kg Met, (4) ligature + 100 mg/kg Met, and (5) ligature + 200 mg/kg Met. Water or Met was administered orally. Maxillae were fixed and scanned using Micro-computed Tomography (µCT) to quantitate linear and bone volume/tissue volume (BV/TV) volumetric bone loss. Histopathological characteristics were assessed through immunohistochemical staining for MMP-9, COX-2, the RANKL/RANK/OPG pathway, SOD-1, and GPx-1. Additionally, confocal microscopy was used to analyze osteocalcin fluorescence. UV-VIS analysis was used to examine the levels of malondialdehyde, glutathione, IL-1ß and TNF-α from gingival tissues. Quantitative RT-PCR reaction was used to gene expression of AMPK, NF-κB (p65), and Hmgb1 from gingival tissues. Significance among groups were analysed using a one-way ANOVA. A p-value of p<0.05 indicated a significant difference. RESULTS: Treatment with 50 mg/kg Met significantly reduced concentrations of malondialdehyde, IL-1ß, and TNF-α (p < 0.05). Additionally, weak staining was observed for COX-2, MMP-9, RANK, RANKL, SOD-1, and GPx-1 after 50 mg/kg Met. OPG and Osteocalcin showed strong staining in the same group. Radiographically, linear measurements showed a statistically significant reduction in bone loss after 50 mg/kg Met compared to the ligature and Met 200 mg/kg groups. The same pattern was observed volumetrically in BV/TV and decreased osteoclast number (p<0.05). RT-PCR showed increased AMPK expression and decreased expression of NF-κB (p65) and HMGB1 after 50 mg/kg Met. CONCLUSIONS: Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.

Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT) on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1) nonligated, water; (2) ligated, water; (3) ligated, 1 mg/kg AZT; (4) ligated, 5 mg/kg AZT; and (5) ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1ß, IL-10, TNF-α, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05) and IL-1ß (p<0.05), increased levels of IL-10 (p<0.05), and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.