AIM: To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS: Gastric mucosal injury was induced ...AIM: To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS: Gastric mucosal injury was induced in male Hos:Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-8 and myeloperoxidase (MPO) in mucosal tissues. RESULTS: Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h after oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose- dependent manner. The mucosal concentrations of proinflammatory cytokines (TNF-α, IL-1β, and IL-8) and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacin- treated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION: The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.展开更多
AIM: To examine the effects of adenosine and A1 re- ceptor activation on reperfusion-induced small intestinal injury. METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and system...AIM: To examine the effects of adenosine and A1 re- ceptor activation on reperfusion-induced small intestinal injury. METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclo- pentyladenosine, A1 receptor agonist or 8-cyclopentyl- 1,3-dipropylxanthine, A1 receptor antagonist, plus ade- nosine before ischemia. Following reperfusion, contra- ctions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured. RESULTS: Ischemia significantly decreased both contra- ction and reduced glutathione level which were ameliora- ted by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolis- hed by pretreatment with A1 receptor antagonist. CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal in- jury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.展开更多
文摘AIM: To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS: Gastric mucosal injury was induced in male Hos:Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-8 and myeloperoxidase (MPO) in mucosal tissues. RESULTS: Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h after oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose- dependent manner. The mucosal concentrations of proinflammatory cytokines (TNF-α, IL-1β, and IL-8) and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacin- treated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION: The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.
基金Zonguldak Karaelmas University Research Proje-cts Fund, No. 2003-01-09
文摘AIM: To examine the effects of adenosine and A1 re- ceptor activation on reperfusion-induced small intestinal injury. METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclo- pentyladenosine, A1 receptor agonist or 8-cyclopentyl- 1,3-dipropylxanthine, A1 receptor antagonist, plus ade- nosine before ischemia. Following reperfusion, contra- ctions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured. RESULTS: Ischemia significantly decreased both contra- ction and reduced glutathione level which were ameliora- ted by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolis- hed by pretreatment with A1 receptor antagonist. CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal in- jury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.
