allopurinol and Mesenteric-Vascular-Occlusion

Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion.. Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk.. Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05).. This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

Topics: Animals; Anticoagulants; Edema; Fibrin Fibrinogen Degradation Products; Glutathione; Glutathione Reductase; Interleukin-6; Intestinal Mucosa; Male; Malondialdehyde; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Nitrates; Nitrites; Peroxidases; Protein C; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Warm Ischemia; Xanthine Oxidase

To study the effect of oral administration of a nitric oxide (NO) donor L-arginine (L-Arg), a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats.. Male Wistar rats receivedper os L-Arg (800 mg/kg) or L-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1), L-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8), L-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured.. After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1) groups compared with group C but not in L-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in L-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8), L-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group.. The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of L-Arg but not after administration of L-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os supplementation of L-Arg or Allo in intestinal I/R.

Topics: Administration, Oral; Allopurinol; Animals; Arginine; Catalase; Disease Models, Animal; Enzyme Inhibitors; Intestinal Mucosa; Intestines; Male; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Rats; Rats, Wistar; Reperfusion Injury; Time Factors; Xanthine Oxidase

Production of free radical species in cells and body tissues is known to cause many pathological disorders. Therefore, free radical scavengers play an important role in the prevention of various human diseases. Bamboo grass, Sasa senanensis, is a native Japanese plant. Sasa has been used for medicine in Japan for many centuries. In this study, we investigated the antioxidative activity of Absolutely Hemicellulose Senanensis (AHSS), a novel extract from Sasa. In the first part of this study, we found that AHSS has antioxidant activities by the assay using superoxide anion-2-methyl-6-methoxyphenylethynylimidazopyrazynone (MPEC) reaction kit. We then confirmed its antioxidative activity using a rat ischemia and subsequent reperfusion (I/R) injury model. Breakdown of the intestinal wall caused by intestinal I/R was attenuated by pretreatment with AHSS. Moreover, AHSS inhibited the production of lipid peroxide by intestinal I/R. AHSS could be an important source of ingredients for use in functional foods and other applications.

Topics: Allopurinol; Animals; Antioxidants; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Intestine, Small; Lipid Peroxides; Luminescence; Male; Mesenteric Vascular Occlusion; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury; Sasa; Xanthine Oxidase

A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.

Topics: Allopurinol; Animals; Antioxidants; Arterioles; Ascorbic Acid; Aspirin; Blood Coagulation; Blood Platelets; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fibrinolytic Agents; Free Radicals; Heparin; Male; Mesenteric Vascular Occlusion; Microscopy; Oxygen; Photochemistry; Rats; Rats, Wistar; Rose Bengal; Singlet Oxygen; Videotape Recording; Vitamin E

The intestinal reperfusion injury has been studied in Sprague-Dawley rats weighing 200 g. Intestinal ischemia has been induced by clamping the Superior Mesenteric Artery (SMA) for 120 minutes. In order to parallel clinical situations, free radical scavengers (allopurinol [ALLO]) and superoxide-dismutase [SOD] were inoculated at a low perfusion rate through the femoral vein during the last 20 minutes of the ischemic period. Both drugs have decreased the mortality rate (from 70% in control group, to 40%) and the mean percentage of damaged intestine (30.89% vs. 23.84% and 24.70%). Histologically, ALLO was less effective than SOD (12.54 control; 8.40 SOD; 11.54 ALLO). The modification of glucose, SGOT, SGPT and LDH found in all the ischemic animals shows the hepatocellular injury induced by intestinal reperfusion.

Topics: Allopurinol; Animals; Antioxidants; Female; Free Radical Scavengers; Liver Function Tests; Mesenteric Arteries; Mesenteric Vascular Occlusion; Rats; Rats, Inbred Strains; Reperfusion Injury; Superoxide Dismutase

Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6'-methylene-bis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemia.

Topics: Allopurinol; Animals; Antioxidants; Dogs; Female; Free Radicals; Histamine; Histamine Release; Ileum; Ischemia; Male; Mesenteric Vascular Occlusion; Oxygen; Quinolines; Reperfusion Injury