Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines ...and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control), group II (vehicle control), and group III (resveratrol). Systemic resveratrol (30 mg/kg/day) was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3) and epithelium-derived cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05). The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05). The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05). Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.
Vascular endothelial growth factor (VEGF) is an important mediator of the neoangiogenesis component of remodeling in asthma.
To evaluate the influence of VEGF blockage on airway remodeling, ...specifically epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness, in a mouse model of chronic asthma.
We used 30 BALB/c mice. The control group was not exposed to ovalbumin or any medication (group 1). Other groups were exposed to intraperitoneal and inhaled ovalbumin to achieve chronic asthma. Each of these groups received intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or intraperitoneal bevacizumab (group 4). Histomorphologic examination for epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness was performed from the middle zone of the left lung.
Treatment with anti-VEGF caused significant reduction in epithelial, subepithelial muscle, and basement membrane thickness compared with untreated asthmatic mice (P = .001, P = .03, and P = .009, respectively). Goblet and mast cell numbers were significantly lower in mice treated with anti-VEGF than in untreated mice (P = .02 and P = .007, respectively). Dexamethasone treatment resulted in improvement of all histomorphologic markers, except goblet cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement membrane thickness and mast and goblet cell numbers did not differ (P > .05), but subepithelial muscle layer was thinner in the former (P = .003).
VEGF blockage may provide adjunctive therapeutic options as steroid-sparing agents for more effective treatment of remodeling in asthma.
The aim of this study was to investigate the effects of a specific diet, containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine (HMB/Glu/Arg), on chemoradiation-induced injuries of ...the rat gastrointestinal mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation (n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD) containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group, the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5-FU treatment, feeding with either the standard rat diet or specific diet continued as before. All animals were sacrificed on day 4 after irradiation and 5-FU treatment. Data collected included microbiological, histological and immunohistochemical end points. We found that bacterial colony counts in the ceca and mesenteric lymph nodes of irradiated rats treated with 5-FU were significantly lower in the specific diet (SpD) group than in the standard diet group (P = 0.002–0.05). Morphometrically, gastric, duodenal and colonic mucosal injuries were less severe in the irradiated animals fed the specific diet, as well as the 5-FU-treated animals fed the specific diet, compared to the similarly treated standard diet groups. Apoptosis, measured by TUNEL, revealed significantly lower numbers of TUNEL positive cells in irradiated animals fed the specific diet, and irradiated animals treated with 5-FU and fed the specific diet compared to irradiated animals fed the standard diet, and irradiated animals treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group, the extent of apoptosis was significantly lower than that of the 5-Fu-treated and standard diet group in both the stomach and duodenum (P = 0.0001), but not in the colon. Apoptosis, measured by caspase 3 staining, was significantly less in all three organs of the SpD groups. In conclusion, these findings suggest that a diet supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced gastrointestinal injury, coinciding with reduced bacterial growth.
AIM: To investigate the effects of nilotinib in a rat model of indomethacin-induced enterocolitis.METHODS: Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of ...Laboratory Animal Science were divided into the following three groups: control(n = 7), indomethacin(n = 7) and nilotinib(n = 7). A volume of 0.25 m L of physiological serum placebo was administered to the control and indomethacin groups through an orogastric tube for 13 d. To induce enterocolitis, the indomethacin and nilotinib groups received 7.5 m L/kg indomethacin dissolved in 5% sodium bicarbonate and administered subcutaneously in a volume of 0.5 m L twice daily for three days. Nilotinib was administered 20 mg/kg/d in two divided doses to the nilotinib group of rats for 13 d through an orogastric tube, beginning on the same day as indomethacin administration. For 13 d, the rats werefed a standard diet, and their weights were monitored daily. After the rats were sacrificed, the intestinal and colonic tissue samples were examined. The macroscopic and microscopic pathology scores were evaluated. The pathologist stained all tissue samples using terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick-end labeling method. Mucosal crypts and apoptotic cells were quantified. The plateletderived growth factor receptor(PDGFR) α and β scores assessed by immunohistochemical staining method and tissue and serum tumor necrosis factor(TNF) α levels were determined by enzyme-linked immunosorbent assay. RESULTS: Between days 1 and 13, the rats in the nilotinib and indomethacin groups lost significantly more weight than the controls(-11 g vs +14.14 g, P = 0.013;-30 g vs +14.14 g, P = 0.003). In the small intestinal and colonic tissues, the macroscopic scores were significantly lower in the nilotinib group than in the indomethacin group(1.14 ± 0.38 and 7.29 ± 2.98, P = 0.005; 1.14 ± 0.38 and 7.43 ± 2.64, P = 0.001, respectively), but the values of the nilotinib and indomethacin groups were similar to the control group. In the small intestinal and colonic tissues, the microscopic scores were significantly lower in the nilotinib group than in the indomethacin group(3.43 ± 2.99 and 7.67 ± 3.67, P = 0.043; 2.29 ± 0.76 and 8.80 ± 2.68, P = 0.003, respectively), but the values were similar to the control group. The PDGFR β scores in the small intestine and colon were significantly lower in the nilotinib group than in the indomethacin group(1.43 ± 0.79 and 2.43 ± 0.54, P = 0.021; 1.57 ± 0.54 and 3 ± 0, P =0.001), and the values were similar to controls. The colonic PDGFR α scores were significantly lower in the nilotinib group than in the indomethacin group(1.71 ± 0.49 and 3 ± 0, P = 0.001). The colonic apoptosis scores were significantly lower in the controls than in the nilotinib group(1.57 ± 1.13 and 4 ± 1.29, P = 0.007). Furthermore, the serum and tissue TNF-α levels were similar between the nilotinib and indomethacin groups.C O N C L U S I O N : In the indomethacin-induced enterocolitis rat model, nilotinib has a positive effect on the macroscopic and microscopic pathologic scores, ensuring considerable mucosal healing. Nilotinib decreases PDGFR α and β levels and increases the colonic apoptotic scores, but it has no significant effects on weight loss and the TNF-α levels.
Objective: Detection/localization of infection and inflammation is important for the initiation of correct treatment as well as its maintenance. Nuclear medicine imaging methods play an important ...role in determining infection and inflammation. 18F-2’-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is highly sensitive in such cases when used with tomographic cross-sections. In this study, the development and progression of infection and inflammation were monitored on rats by using 18F-FDG via PET/CT.
Methods: Sterile and infected abscesses were formed on rats using turpentine and S. aureus, respectively. For evaluation of the formation and progression of the abscess, 18F-FDG was injected into the rats and they were imaged by PET/CT at intervals of twenty-four hours for five days. Maximum standard uptake value (SUVmax) of 18F-FDG was calculated.
Results: The highest activity involvement was seen on the first day of abscess formation. On the first day, SUVmax of the S. aureus abscess was 3.9±0.9 while in the sterile abscess SUVmax in the first day was 2.2±0.8. 18F-FDG uptake decreased day by day and it reached the background level on the fourth and fifth days. There were statistically significant differences between S. aureus and sterile abscess, and between sterile abscess and background activity in terms of SUVmax values during the first three days (p<0.05). On the fourth and fifth days, there was no statistically significant difference between S. aureus and sterile abscess, and between sterile abscess and background activity (p>0.05).
Conclusion: The results demonstrated that the SUVmax value for 18F-FDG can be useful in the early differentiation of sterile and infected abscess. In addition, 18F-FDG-PET imaging has the advantage of local availability of equipment and labeled agents leading rapid diagnosis of differentiation of infection and inflammation.
Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. ...In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-γ IL-2 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.
Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO) in asthma. As, it is suggested that L-arginine may ...have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂) and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control). All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I), saline (Group II) and budesonide (Group III), respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL) was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043). Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05). Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.
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