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Recent studies demonstrated that the proanthocyanidins (PA), the polymers of flavan-3-ols, naturally occurring plant metabolites widely available in fruits, vegetables, nuts, seeds, flowers and bark, have anti-inflammatory, anticarcinogenic, anti-allergic, antioxidant and vasodilatory actions. We hypothesized that Viburnum opulus PA (VOPA, Caprifoliaceae), due to activation of multifactorial gastrointestinal mucosal defense mechanisms, exert gastroduodenoprotective effects. The aim of the study was: 1) to investigate VOPA effects on gastroduodenal mucosal integrity and pattern of carbohydrate binding proteins and nitric oxide (NO) content in intact mucosa and that exposed to non-topical ulcerogens (stress) in rats without and with capsaicin (125 mg/kg, sc) denervation; and 2), to assess the role of activity of antioxidizing enzymes superoxide dismutase (SOD), catalase (CAT), gluthatione peroxidase (GPx) in VOPA-iduced gastroduodenoprotection against water immersion and restraint stress (WRS) in rats. VOPA was administered orally in dose of 25, 50 or 75 mg/kg body weight. Gastroduodenal mucosal damage detected by routine light microscopic investigation and lectin histochemistry set, purified from plant and animal sources of Carpatian region. NO content, pro-and antioxidant system were determinated by routine laboratory methods. Pretreatment with VOPA afforded gastroduodenoprotection and was accompanied by an increase in NO expression, both changes being reversed by sensory denervation, as well as by the rise of SOD, CAT activity and fall in MDA content. Our study shows that VOPA exerts a potent gastroduodenoprotective activity via an increase in endogenous NO generation, suppression of lipid peroxidation and mobilization of antioxidant activity and changes in glycoconjugate content of the gastroduodenal mucosa of rat.
Melatonin (MT) is known to protect gastrointestinal mucosa against various types of injury but its effects on esophageal damage have not been studied. We examined the effects of MT on acute esophageal injury and the mechanism involved in the action of this indole. Acute esophageal lesions were induced by perfusion with acid-pepsin solution using tube inserted through the oral cavity into the mid of esophagus of anaesthetized rats with or without inhibition of prostaglandin (PG) generation by indomethacin (5 mg/kg/day), nitric oxide (NO) formation by NG-nitro-L-arginine (L-NNA, 20 mg/kg/day) or sensory nerves deactivation by capsaicin (125 mg/kg, sc). The esophageal injury was assessed by macroscopic score and histologic activity index. The esophageal mucosal blood flow (EBF) was determinated by H2-gas clearance method. The plasma TNF-alpha and nitrate/nitrite (NOx) levels and mucosal PGE2 contents were assessed by immunoassays. Esophageal acid-pepsin perfusion induced noticeable esophageal mucosal injury as compared to perfusion with vehicle saline. The pretreatment with MT prevented significantly esophageal injury, raised EBF and mucosal content of PGE2, while decreasing the levels of TNF-alpha. Inhibition of COX/PG and NOS/NO systems by indomethacin and L-NNA, respectively, or inactivation of sensory nerves by capsaicin, that manifested in further increase of esophageal injury, reduced the levels of EBF, markedly raised the levels TNF-alpha and reduced mucosal PGE2, but the pretreatment with MT prevented significantly esophageal injury, improved EBF and raised mucosal PGE2 contents. These studies suggest that MT can be considered as a novel esophagoprotector, acting, at least in part, through the COX/PG and NOS/NO systems and activation of sensory nerves.
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