Ischemic preconditioning reduces caspase-related intestinal apoptosis.
ABSTRACT To investigate the preventive effect of ischemic preconditioning (IPC) on ischemia/reperfusion (I/R)-induced apoptosis and injury in the rat intestine.
We divided 30 male Wistar rats, weighing 300-350 g, randomly into three groups. The control group rats (n = 10) were subjected to laparotomy only; the I/R group (n = 10) rats were subjected to occlusion of the superior mesenteric artery for 45 min, followed by reperfusion for 60 min; and the IPC group (n = 10) rats were subjected to IPC, achieved with two cycles of 5 min ischemia and 5 min reperfusion immediately before the I/R, as in the I/R group. Blood samples were collected by cardiac puncture, to measure nitrate and myeloperoxidase (MPO) levels. Histopathological and immunohistochemical studies were done to evaluate the I/R-induced apoptosis and injury.
The blood MPO and nitrate levels were increased in the I/R group, but IPC prevented their increase. There were significantly fewer apoptotic cells in the IPC group than in the I/R group, and this finding was supported by the caspase-3 expression in the ileum. The intestinal histopathology was also protected by IPC against I/R-induced injury.
Ischemic preconditioning clearly prevented I/R-induced injury and apoptosis by a mechanism related to the caspase-3-dependent pathway. We also showed that IPC inhibited leukocyte activation, with the suppression of myeloperoxidase levels in I/R and nitric oxide-related oxidoinflammatory pathway upregulation.
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ABSTRACT: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury. Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N(6)-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured. Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist. The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.World Journal of Gastroenterology 02/2007; 13(4):538-47. · 2.55 Impact Factor
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ABSTRACT: We investigated whether Tempol, a water-soluble antioxidant, prevents the harmful effects of superior mesenteric ischemia/reperfusion on intestinal tissues in rats. The rats were divided into three groups of 10. In group 1, the superior mesenteric artery (SMA) was isolated but not occluded, and in groups 2 and 3 the superior mesenteric artery was occluded for 60 min. After that, the clamp was removed and reperfusion began. In group 3, 5 min before the start of reperfusion, a bolus dose of 30 mg/kg Tempol was administered intravenously and continued at a dose of 30 mg/kg for 60 min. All animals were euthanized after 24 h and tissue samples were collected for analysis. There was a significant increase in myeloperoxidase activity, malondialdehyde levels, and the incidence of bacterial translocation in group 2, with a decrease in glutathione levels. These parameters were found to be normalized in group 3. The intestinal mucosal injury score in group 2 was significantly higher than those in groups 1 and 3. Tempol prevents bacterial translocation while precluding the harmful effects of ischemia/reperfusion injury on intestinal tissues in a rat model of superior mesenteric artery occlusion.Surgery Today 02/2009; 39(5):407-13. · 0.96 Impact Factor
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ABSTRACT: Intestinal ischemia/reperfusion (IR) injury involves activation of inflammatory mediators, mucosal necrosis, ileus, and alteration in a variety of gene products. Ischemic preconditioning (IPC) reduced all the effects of intestinal injury seen in IR. In an effort to investigate the molecular mechanisms responsible for the protective effects afforded by IPC, we sought to characterize the global gene expression pattern in rats subjected to IPC in the setting of IR injury. Rats were randomized into five groups: (1) Sham, (2) IPC only (3) IR, (4) Early IPC + IR (IPC --> IR), and (5) Late IPC + IR (IPC --> 24 h --> IR). At 6 h after reperfusion, ileum was harvested for total RNA isolation, pooled, and analyzed on complementary DNA (cDNA) microarrays with validation using real-time polymerase chain reaction (PCR). Significance Analysis of Microarray (SAM) software was used to determine statistically significant changes in gene expression. Early IPC + IR had 5,167 induced and 4 repressed genes compared with the other groups. SAM analysis revealed 474 out of 10,000 genes differentially expressed among the groups. Early and Late IPC + IR had more genes involved in redox hemostasis, the immune/inflammatory response, and apoptosis than either the IPC only or IR alone groups. The transcriptional profile suggests that IPC exerts its protective effects by regulating the gene response to injury in the intestine.Digestive Diseases and Sciences 09/2009; 55(7):1866-77. · 2.26 Impact Factor