Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to investigate the protective effect of the pineal secretary product melatonin in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were sacrificed for tissue histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAO-shocked rats developed a significant increase of tissue myeloperoxidase and malondialdehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 hr after reperfusion). Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localized in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. Melatonin (applied at 3 mg/kg, 5 min prior to reperfusion, followed by an infusion of 3 mg/kg per hr), significantly reduced ischemia reperfusion injury in the bowel as evaluated by histological examination. This prevented the infiltration of neutrophils into the reperfused intestine, is evidenced by reduced myeloperoxidase activity and reduced lipid peroxidation. This was evaluated by malondialdehyde activity which reduced the production of peroxynitrite during reperfusion, markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats and improved their survival. Taken together, our results clearly demonstrate that melatonin treatment exerts a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury.
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PMID:Beneficial effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion. 1062 2

The aim of the present study was to investigate the protective effect of the peroxynitrite decomposition catalyst 5,10,15, 20-tetrakis(2,4,6-trimethyl-3,5-disulfonatophenyl)-porphyrinato iron (III) (FeTMPS) in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAO-shocked rats developed a significant increase of tissue myeloperoxidase and malonaldehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin localized mainly in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats and stained with antibody to ICAM-1 showed a diffuse staining. Administration of FeTMPS significantly reduced ischemia/reperfusion injury in the bowel, and reduced lipid and the production of peroxynitrite during reperfusion. Treatment with PN catalyst also markedly reduced the intensity and degree of P-selectin and ICAM-1 staining in tissue sections from SAO-shocked rats and improved survival. Our results clearly demonstrate that peroxynitrite decomposition catalysts exert a protective effect in SAO and that this effect may be due to inhibition of the expression of adhesion molecules and the tissue damage associated with peroxynitrite-related pathways.
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PMID:Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. 1083 27

Protective role of selenium against free radical damage was first demonstrated in the heart and this effect was further questioned in other systems. In the present study, the effects of exogenously administered selenium on intestinal fine morphology, lipid peroxidation, and bacterial translocation (BT) in experimental intestinal ischemia/reperfusion (I/R) model were examined. Thirty-two male Wistar rats weighing 250-300 g were randomized into four groups. Sham group (n=8) underwent laparotomy only. In the I/R group (n=8), laparotomy was performed and the superior mesenteric artery was occluded using an atraumatic microvascular clamp for 30 min. In corresponding selenium-treated groups (n=8 each), sodium selenate was given 0.2 mg kg(-1)day(-1) intraperitoneally (i.p.) for 3 consecutive days, prior to surgery for either laparotomy only or with I/R. Twenty-four hours later, tissue samples from liver, spleen, and mesenteric lymph nodes were obtained under sterile conditions for microbiological analysis and further evaluation of I/R-induced intestinal injury. Ileum samples were fixed in 10% formaldehyde for histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, and liver was significantly higher than other groups (P<0.05). Selenium supplementation prevented I/R-induced BT and significantly reduced the I/R-induced intestinal injury (P<0.05). Tissue MDA levels from the ileum specimens of selenium-treated rats were significantly lower than that of the I/R group (P<0.05). Our results provide evidence that the relationship between BT and lipid peroxidation in intestinal tissue is crucial. Selenium pretreatment reduces lipid peroxidation which contributes to the maintenance of intestinal mucosal integrity.
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PMID:Selenium pretreatment prevents bacterial translocation in rat intestinal ischemia/reperfusion model. 1222 Sep 57

It is suggested that gastrointestinal mucosal blood flow depends on a balanced release of vasoactive substances from the endothelium. The present study investigated the effects of molsidomine on the small intestine after ischemia-reperfusion (I/R) injury in four groups of 10 rats each composed: (1) SO, sham operation; (2) untreated I/R; (3) ML, I/R plus molsidomine pretreatment; (4) L-NAME, I/R plus N-omega-nitro-L-arginine methyl ester pretreatment. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileum specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histologic changes. Mean MDA levels in the SO, untreated I/R, ML, and L-NAME groups were 95.60 +/- 2.59, 136.90 +/- 4.35, 121.10 +/- 3.38, and 137.40 +/- 4.42 nmol/g wet tissue, respectively. Although the MDA level in the ML group was higher than in the SO group ( P < 0.0001), it was significantly lower compared to the untreated I/R and L-NAME groups ( P < 0.0001, P < 0.0001). Mucosal injury scores (MIS) in groups 1-4 were 0.2 +/- 0.42, 3.9 +/- 0.73, 1.5 +/- 0.70, and 4.1 +/- 0.56, respectively. In group 3 the MIS was significantly lower than in groups 2 and 4 ( P < 0.0001, P < 0.0001). Molsidomine plays a role in attenuating reperfusion injury of the small intestine by depression of tissue MDA levels and MIS and regulates post-ischemic intestinal perfusion while restoring the intestinal microcirculatory blood flow and histologic injury.
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PMID:The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine. 1278 56

Cyclooxygenase (COX)-2 has been identified as an important mediator elaborated during ischemia/reperfusion, with pro- and anti-inflammatory properties having been reported. As the role of COX-2 in the small intestine remains unclear, we hypothesized that COX-2 expression would mediate mesenteric ischemia/reperfusion-induced gut injury, inflammation, and impaired transit and that these deleterious effects could be reversed by the selective COX-2 inhibitor, N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulphanamide (NS-398). Additionally, we sought to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in mediating protection by NS-398 in this model. Rats underwent sham surgery or were pretreated with NS-398 (3, 10, or 30 mg/kg) intraperitoneally 1 h before 60 min of superior mesenteric artery occlusion and 30 min to 6 h of reperfusion. In some experiments, NS-398 (30 mg/kg) was administered postischemia. Ileum was harvested for COX-2 mRNA and protein, PGE2, myeloperoxidase (inflammation), histology (injury), intestinal transit and PPARgamma protein expression, and DNA-binding activity. COX-2 expression and PGE2 production increased after mesenteric ischemia/reperfusion and were associated with gut inflammation, injury, and impaired transit. Inhibition of COX-2 by NS-398 (30 mg/kg, but not 3 or 10 mg/kg) not only reversed the deleterious effects of COX-2, but additionally induced expression and nuclear translocation of PPARgamma. NS-398 given postischemia was equally protective. In conclusion, COX-2 may function as a proinflammatory mediator in a rodent model of mesenteric ischemia/reperfusion. Reversal of gut inflammation, injury, and impaired transit by high-dose NS-398 is associated with PPAR activation, suggesting a potential role for PPAR-gamma in shock-induced gut protection.
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PMID:Peroxisome proliferator-activated receptor gamma mediates protection against cyclooxygenase-2-induced gut dysfunction in a rodent model of mesenteric ischemia/reperfusion. 1624 33

In this study, we evaluated the effect of tyrphostin AG126, a tyrosine kinase inhibitor, in the splanchnic artery occlusion (SAO) shock mediated injury. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO shocked rats developed a significant fall in mean arterial blood pressure. Ileum analysis revealed that SAO shock is characterized by a significant (P<0.01) induction in TNF-alpha and IL-1 ileum levels, while immunohistochemistry examination of necrotic ileum demonstrated a marked increase in the immunoreactivity in intracellular adhesion molecule (ICAM-1) and nitrotyrosine formation. A significant increase in myeloperoxidase activity (P<0.01) was also observed in rats subjected to ischemia-reperfusion injury. Tyrphostin AG126, given intraperitoneally 30 min before ischemia at the dose of 5 mg/kg, significantly improved mean arterial blood pressure, markedly reduced TNF-alpha and IL-1beta levels and the positive staining of ICAM-1 into the reperfused ileum. Tyrphostin AG126 significantly improved the histological status of the reperfused tissue. In conclusion, this study demonstrates that tyrphostin AG126 exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock and suggests that this tyrosine kinase inhibitor may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury.
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PMID:Tyrphostin AG 126 reduces intestinal ischemia-reperfusion injury in the rat. 1648 31

Heme oxygenase (HO) represents the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron, and biliverdin. Recent evidence suggests that several of the beneficial properties of HO, may be linked to CO. The objectives of this study were to determine if low-dose inhaled CO reduces remote intestinal leukocyte recruitment, proinflammatory cytokine expression, and oxidative stress elicited by hindlimb ischemia-reperfusion (I/R). Male mice underwent 1 h of hindlimb ischemia, followed by 3 h of reperfusion. Throughout reperfusion, mice were exposed to AIR or AIR + CO (250 ppm). Following reperfusion, the distal ileum was exteriorized to assess the intestinal inflammatory response by quantifying leukocyte rolling and adhesion in submucosal postcapillary venules with the use of intravital microscopy. Ileum samples were also analyzed for proinflammatory cytokine expression [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta] and malondialdehyde (MDA) with the use of enzyme-linked immunosorbent assay and thiobarbituric acid reactive substances assays, respectively. I/R + AIR led to a significant decrease in leukocyte rolling velocity and a sevenfold increase in leukocyte adhesion. This was also accompanied by a significant 1.3-fold increase in ileum MDA and 2.3-fold increase in TNF-alpha expression. Treatment with AIR + CO led to a significant reduction in leukocyte recruitment and TNF-alpha expression elicited by I/R; however, MDA levels remained unchanged. Our data suggest that low-dose inhaled CO selectively attenuates the remote intestinal inflammatory response elicited by hindlimb I/R, yet does not provide protection against intestinal lipid peroxidation. CO may represent a novel anti-inflammatory therapeutic treatment to target remote organs following acute trauma and/or I/R injury.
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PMID:Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory response elicited by hindlimb ischemia-reperfusion. 1911 81