Current Issue : October - December Volume : 2019 Issue Number : 4 Articles : 5 Articles
Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of\neosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for\nupper AHR (UAHR) in rodents is poorly developed, although measurements of nasal resistance\nhave been reported. Here we assessed UAHR by direct measurement of swelling of the nasal\nmucosa induced by intranasal methacholine (MCh) using micro-computed tomography (micro-CT).\nMicro-CT analysis was performed in both naïve and ovalbumin-induced AR mice following intranasal\nadministration of MCh. The nasal cavity was segmented into two-dimensional horizontal and axial\nplanes, and the data for nasal mucosa were acquired for the region of interest threshold. Then, a ratio\nbetween the nasal mucosa area and nasal cavity area was calculated as nasal mucosa index. Using\nour novel method, nasal cavity structure was clearly identified on micro-CT, and dose-dependent\nincreased swelling of the nasal mucosa was observed upon MCh treatment. Moreover, the nasal\nmucosa index was significantly increased in AR mice compared to controls following MCh treatment,\nwhile ovalbumin administration did not affect swelling of the nasal mucosa in either group. This\nUAHR following MCh treatment was completely reversed by pretreatment with glucocorticoids.\nThis novel approach using micro-CT for investigating UAHR reflects a precise assessment system for\nswelling of the nasal mucosa following MCh treatment; it not only sheds light on the mechanism of\nAR but also contributes to the development of new therapeutic drugs in AR patients....
Background: UV exposure-induced oxidative stress is implicated as a driving mechanism\nfor melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation.\nAccordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination\nwith the epigenetic drug 5-aza-2â??-deoxycytidine (DAC) could slow melanoma cell growth. SFN is\na natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase\ninhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone\nepigenetic modifications were measured after single and combination treatments with SFN and\nDAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression\nprofiles upon combinational treatments with SFN and DAC, while no significant alterations in histone\nepigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator\ncytokine--C-C motif ligand 5 (CCL-5)--was validated. Conclusions: These results indicate a potential\ncombinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling\nmelanoma cell growth....
Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a\npotent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of\nantioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous\nmelatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley\nmale rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group)\nor the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group).\nThe effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in\nserum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in\nall three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine\nand thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in\nserum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations\nwere decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate\ndehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum:\nNO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but\nconcentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both\nin serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in\nserum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were\nless severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of\nmelatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and\nhistopathological lesions in the liver in rats with CCl4-induced hepatitis....
Drug-induced liver injury (DILI) is one of the most serious and frequent drug-related adverse\nevents in humans. Selenium (Se) and glutathione (GSH) have a crucial role for the hepatoprotective\neffect against reactive metabolites or oxidative damage leading to DILI. The hepatoprotective capacity\nrelated to Se and GSH in rodents is considered to be superior compared to the capacity in humans.\nTherefore, we hypothesize that Se/GSH-depleted rats could be a sensitive animal model to predict DILI\nin humans. In this study, Se-deficiency is induced by feeding a Se-deficient diet and GSH-deficiency is\ninduced by l-buthionine-S,R-sulfoxinine treatment via drinking water. The usefulness of this animal\nmodel is validated using flutamide, which is known to cause DILI in humans but not in intact rats.\nIn the Se/GSH-depleted rats from the present study, decreases in glutathione peroxidase-1 protein\nexpression and GSH levels and an increase in malondialdehyde levels in the liver are observed\nwithout any increase in plasma liver function parameters. Five-day repeated dosing of flutamide at\n150 mg/kg causes hepatotoxicity in the Se/GSH-depleted rats but not in normal rats. In conclusion,\nSe/GSH-depleted rats are the most sensitive for detecting flutamide-induced hepatotoxicity in all the\nreported animal models....
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is recognized as a critical regulator\nin physiological and pathophysiological processes of atherosclerosis (AS). However, the underlying\nmechanism remains unclear. As the precursor cells of endothelial cells (ECs), endothelial progenitor\ncells (EPCs) can prevent AS development through repairing endothelial monolayer impaired by\nproatherogenic factors. The present study investigated the effects of S1P on the biological features of\nmouse bone marrow-derived EPCs and the underlying mechanism. The results showed that S1P\nimproved cell viability, adhesion, and nitric oxide (NO) release of EPCs in a bell-shaped manner,\nand migration and tube formation dose-dependently. The aforementioned beneficial eects of S1P\non EPCs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor of LY294002 and\nnitric oxide synthase (NOS) inhibitor of Nâ??-nitro-L-arginine-methyl ester hydrochloride (L-NAME).\nThe inhibitor of LY294002 inhibited S1P-stimulated activation of phosphorylated protein kinase B\n(AKT) (p-AKT) and endothelial nitric oxide synthase (eNOS) (p-eNOS), and down-regulated the level\nof eNOS significantly. The results suggest that S1P improves the biological features of EPCs partially\nthrough PI3K/AKT/eNOS/NO signaling pathway....
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