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 relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
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PMID:Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. 920 Oct 88

The effect of a high fat diet (HFD) on renal function, renal mitochondrial function and intrarenal oxygen-free radial scavenging activity were examined in the ischemia-reperfusion model of the rat kidney. Whether of not a novel lipophilic antioxidant (BO653) could minimize this effect in vivo was also investigated. Thirty minutes renal ischemia was introduced by vascular clamp in rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653 by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45% decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute ischemia deteriorated the mitochondrial function in the normal diet (ND) group, high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty-minute reperfusion ameliorated the mitochondrial function in all those groups. The kidney content of TBARS was not increased after the ischemia-reperfusion in all these groups. In the HFD group, the kidney content of GPX was higher than in the ND group during ischemia-reperfusion, but in the HFD group, the kidney content of SOD was significantly decreased after the thirty-minute ischemia. Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and BO653 ameliorated this effect judged by creatinine clearance and renal mitochondrial function. Reperfusion injury could not be confirmed in the present model based on the results of lipid peroxidation and oxygen-free radical scavenging enzyme activity.
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PMID:[Effects of high fat diet and a novel antioxidant (BO653) on ischemia reperfusion injury of rat kidney]. 928 10

Melatonin's actions in organisms are more widespread than originally envisaged. Over three decades ago, the changing pattern of nocturnal melatonin production was found to be the signal for the annual cycle of reproduction in photoperiodic species. Since then, melatonin's actions also have been linked to circadian rhythms, immune function, sleep, retinal physiology and endocrine functions in general. In recent years, however, the sphere of influence of melatonin was further expanded when the indole was found to be an effective free radical scavenger and antioxidant. Free radicals are toxic molecules, many being derived from oxygen, which are persistently produced and incessantly attack and damage molecules within cells; most frequently this damage is measured as peroxidized lipid products, carbonyl proteins, and DNA breakage or fragmentation. Collectively, the process of free radical damage to molecules is referred to as oxidative stress. Melatonin reduces oxidative stress by several means. Thus, the indole is an effective scavenger of both the highly toxic hydroxyl radical, produced by the 3 electron reduction of oxygen, and the peroxyl radical, which is generated during the oxidation of unsaturated lipids and which is sufficiently toxic to propagate lipid peroxidation. Additionally, melatonin may stimulate some important antioxidative enzymes, i.e., superoxide dismutase, glutathione peroxidase and glutathione reductase. In in vivo tests, melatonin in pharmacological doses has been found effective in reducing macromolecular damage that is a consequence of a variety of toxic agents, xenobiotics and experimental paradigms which induce free radical generation. In these studies, melatonin was found to significantly inhibit oxidative damage that is a consequence of paraquat toxicity, potassium cyanide administration, lipopolysaccharide treatment, kainic acid injection, carcinogen administration, carbon tetrachloride poisoning, etc., as well as reducing the oxidation of macromolecules that occurs during strenuous exercise or ischemia-reperfusion. In experimental models which are used to study neurodegenerative changes associated with Alzheimer's and Parkinson disease, melatonin was found to be effective in reducing neuronal damage. Its lack of toxicity and the ease with which melatonin crosses morphophysiological barriers and enters subcellular compartments are essential features of this antioxidant. Thus far, most frequently pharmacological levels of melatonin have been used to combat oxygen toxicity. The role of physiological levels of melatonin, which are known to decrease with age, is being investigated as to their importance in the total antioxidative defense capacity of the organism.
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PMID:Melatonin in relation to cellular antioxidative defense mechanisms. 928 72

Superoxide dismutase (SOD) scavenges oxygen radicals that are implicated in the pathogenesis of intestinal ischemia-reperfusion injury. The effect of intestinal ischemia and reperfusion was investigated in transgenic mice overexpressing human Cu-Zn SOD. Ischemia was induced by occluding the superior mesenteric artery. Myeloperoxidase activity was determined as an index of neutrophil infiltration, and malondialdehyde levels were measured as an indicator of lipid peroxidation. Forty-five minutes of intestinal ischemia followed by 4 h of reperfusion caused an increase in intestinal levels of malondialdehyde in both nontransgenic and transgenic mice, but the concentration of malondialdehyde was significantly greater in nontransgenic mice. Intestinal ischemia-reperfusion also caused an increase in intestinal and pulmonary myeloperoxidase activity in nontransgenic and transgenic mice, but the transgenic mice had significantly lower levels of myeloperoxidase activity than nontransgenic mice. Transgenic mice had higher levels of intestinal SOD activity than nontransgenic mice. There were no significant differences in the catalase or glutathione peroxidase activities. In conclusion, our study demonstrates that the overexpression of SOD protects tissues from neutrophil infiltration and lipid peroxidation during intestinal ischemia-reperfusion.
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PMID:Intestinal ischemia and reperfusion injury in transgenic mice overexpressing copper-zinc superoxide dismutase. 935 55

Lipid peroxidation and active oxygen metabolites have been suggested to play an important role in the pathogenesis of acute gastric mucosal injury induced by ischemia-reperfusion. The aim of this study was to examine the in vivo protective effects of melatonin on ischemia-reperfusion induced gastric damage in rats. The peroxidation of lipids and changes in the activities of related enzymes such as glutathione peroxidase and myeloperoxidase, as a marker of neutrophil infiltration, were also studied. Our results show that gastric injury was significantly increased after 30 min ischemia induced by clamping the celiac artery and 60 min reperfusion. Intraperitoneal administration of melatonin prevented postischemic mucosal injury. The mean ulcer indices of rats treated with 5, 10, and 20 mg kg(-1) were significantly lower (P<0.01, P<0.001) than that of control rats. These protective effects were likely in part related to a reduction of neutrophil infiltration (myeloperoxidase values). Lipid peroxidation in the stomach was increased by ischemia-reperfusion injury and this increase was inhibited by the administration of melatonin. In addition, treatment with melatonin limited the decreased glutathione peroxidase activity. The results suggest that melatonin confers a marked protection against ischemia-reperfusion gastric injury which could be due to melatonin's free radical scavenging activity and its ability to reduce neutrophil-induced toxicity.
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PMID:Melatonin protects against gastric ischemia-reperfusion injury in rats. 939 41

The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p < 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p < 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.
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PMID:Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion. 940 79

Reactive oxygen species (ROS) have been implicated in a variety of pathological processes. The generation of highly reactive oxygen metabolites is an integral feature of normal cellular metabolism (mitochondrial respiratory chain, phagocytosis, arachidonic acid metabolism, ovulation and fertilization), however their production can multiply during pathological circumstances. Free oxygen radicals act either on the extracellular matrix or directly upon cellular membranes themselves. The fundamental defense of the organism against ROS include scavenger enzymes (superoxide dismutase, catalase, glutathione peroxidase) and lipid- and water soluble antioxidant compound (ascorbic acid, glutathione, albumin, transferrin, etc.). Their role in ischemia-reperfusion models have now been comprehensively investigated and it has become clear that ROS is to be blamed for the bulk of post-ischemic injuries, hence the basis for newly established antioxidant therapy in such cases. Also more and more studies have concluded a pivotal role of ROS in degenerative and inflammatory conditions, post-radiation processes and aging. Therefore it seems as we are continuously shedding light on the crucial part played by these molecules regarding a wide range of pathologies, we are discovering new therapeutic windows that would clinically assist us in managing such conditions.
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PMID:Oxygen free radicals and their clinical implications. 940 83

The goal of this study was to examine whether chronic administration of propranolol offers protection against ischemia-reperfusion injury and whether it induces any change in the myocardial endogenous antioxidant enzyme activities and their gene expression. Rats were treated with propranolol (10 mg/kg/day, i.p.) for either 6 or 18 days. Forty-eight h after the last propranolol injection, isolated hearts were subjected to 60 min of global ischemia and 40 min of reperfusion. Resting tension in the control and treated groups after ischemia was 385+/-30 and 150+/-15%; and upon reperfusion was 140+/-11 and 49+/-6%, respectively, as compared to the pre-ischemic values. Recovery of the contractile function in globally ischemic hearts upon reperfusion was about 35% in the treated group as compared to about 16% in the control group at 10 and 20 min. A positive response to catecholamine was observed in hearts from propranolol group (C, 3.41+/-0.36; epi, 6.03+/-0.47 g/g) and was comparable to control hearts (C, 3.55+/-0.31; epi, 6.48+/-0.42 g/g). Myocardial antioxidants, catalase and glutathione peroxidase enzyme activities, in the treated group, prior to ischemia-reperfusion were increased by 67+/-9 and 45+/-11%, respectively, over those in controls. Superoxide dismutase activity did not show any change. The mRNA expression for the three antioxidant enzymes did not change in the hearts of the treated group as compared to control. Lipid peroxidation, both before and after the ischemia-reperfusion episode, was significantly reduced in the propranolol-treated hearts compared to the control group. Hearts studied at the end of reperfusion showed no difference in enzyme activities between treated and control groups. These data show that propranolol treatment of the animals protects against ischemia-reperfusion injury in isolated hearts in the absence of beta-blockade. Increased endogenous antioxidant enzyme activities due to propranolol treatment may have a role in this protection.
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PMID:Chronic treatment with propranolol induces antioxidant changes and protects against ischemia-reperfusion injury. 944 39

As stroke is a major cause of disability and death in the western world, there is great interest in the basic mechanisms by which ischemia/reperfusion (I/R) causes damage. To this end, extensive research has been carried out which identifies reactive oxygen species (ROS) as key participants in brain damage resultant from I/R. Brain tissue is protected from ROS damage by antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GP). Overexpression of SOD in transgenic mice has already been demonstrated to confer protection against I/R damage in murine stroke models. We are using transgenic mice overexpressing the intracellular form of glutathione peroxidase (GP1) to determine the protective capacity of overexpression of this enzyme on stroke damage. 1 h of focal cerebral ischemia followed by 24 h of reperfusion was induced using the intraliminal suture method. Volume of infarction was reduced by 48% in GP1 mice compared to nontransgenic littermates. Brain edema was reduced by 33%. Behavioral deficits agreed with histologic data. Overexpression of glutathione peroxidase confers significant protection against I/R damage in our stroke model possibly through direct scavenging of ROS or through the influencing of signalling mechanisms which lead to tissue damage.
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PMID:Overexpression of human glutathione peroxidase protects transgenic mice against focal cerebral ischemia/reperfusion damage. 947 16

The effect of ginsenoside-Rd in ischemic-reperfused rats was examined. In control rats, blood and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to ischemia and reperfusion, the activities of the antioxidation enzymes superoxide dismutase, catalase and glutathione peroxidase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. Decreased levels of urea nitrogen and creatinine in serum demonstrated a protective action against the renal dysfunction caused by ischemia and recirculation. On the other hand, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells subjected to hypoxia-reoxygenation, probably by preventing oxygen free radicals from attacking the cell membranes.
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PMID:A study of ginsenoside-Rd in a renal ischemia-reperfusion model. 949 38


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