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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult male Wistar rats were divided in 3 groups. In the first group, infrarenal abdominal aorta was occluded for 6 hours and reperfused thereafter. In the second group, the reperfusion was not made, and the third group underwent a sham operation. Lysosomal enzymatic activities were assessed in serum tissues. Lysosomal membrane fragilities were estimated also in these tissues. Finally, 14C-aminopyrine breath test (ABT) was studied to define the possible liver dysfunction caused by limb ischemia. As a result, release of lysosomal enzymes from ischemic muscle was confirmed in vitro experiments, and the increase in the serum was statistically significant in the first and second groups as compared to the third group. Particularly prominent was a marked elevation of cathepsin-D in the first group which was observed immediately after the release of occlusion. Results of liver lysosomal enzymes and ABT revealed significant cellular damages and depression of microsomal function of the liver both in the first and second groups. These studies suggest that lysosomal enzymes derived from ischemic muscle exert a possible toxicity on the liver, and liver damage thus resulted may play a roll on the pathogenesis of whole body injury associated with acute and critical lower limb ischemia.
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PMID:[Serum and tissue lysosomal enzymes and liver dysfunction after an experimental acute lower limbs ischemia in the rats]. 144 52

This study was done to determine the relationship between microsomal lipid peroxidation during hepatic ischemia/reperfusion and alteration in cytochrome P-450-dependent drug metabolism. Rats were pretreated with alpha-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham-ischemic animals. After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450 and mixed function oxidases were studied. In vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr (5,242 +/- 682 U/L) and were significantly reduced by alpha-tocopherol pretreatment (1,854 +/- 229 U/L, p less than 0.01). Similarly, microsomal lipid peroxidation was elevated in the vehicle-treated ischemic group, but this elevation was prevented by alpha-tocopherol pretreatment. Microsomal cytochrome P-450 content and aminopyrine-N-demethylase activity were both decreased in vehicle-treated ischemic rats to 60% and 70% of sham-ischemic control levels, respectively. Although alpha-tocopherol restored cytochrome P-450 content to the level of sham-ischemic control rats, aminopyrine-N-demethylase activity remained at 76% of control with alpha-tocopherol treatment (p less than 0.01 compared with sham-ischemic control). In contrast to what was seen with cytochrome P-450 and aminopyrine-N-demethylase, aniline p-hydroxylase activity was elevated in the vehicle-treated ischemic rats compared with sham-ischemic control rats. These increases were prevented by alpha-tocopherol pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alpha-tocopherol on hepatic mixed function oxidases in hepatic ischemia/reperfusion. 173 30

Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused by restoration of blood flow when oxygen free radicals are produced. Cellular sources of oxygen free radicals include the electron transport chain, the microsomal electron transport chain, oxidant enzymes (xanthine oxidase, cyclo-oxygenase), phagocytes, and cellular auto-oxidation of Fe2+ and epinephrine. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy production. Studies in models of acute renal failure have yielded convincing evidence that oxygen free radical production occurs during ischemia/reperfusion. More than a dozen reports have demonstrated the ability of exogenous antioxidants to ameliorate renal injury in vivo. Direct demonstration of increased oxygen free radical production during reoxygenation following hypoxia has been shown in cultured renal epithelial cells. Oxygen free radicals also play a role in toxic acute renal failure. The therapeutic usefulness of free radical scavengers remains to be tested.
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PMID:Oxygen free radicals in acute renal failure. 175 21

Cellular damage of various organs by ischemia following reperfusion is assumed to be at least in part due to lipid peroxidation in biomembranes, and oxygen-derived free radicals play a major role. The level of lipid peroxides in liver tissue increased during 90-min ischemia. When reflow of hepatic blood was allowed, a greater increase in the lipid peroxides was observed. Similar increases were obtained in several serum markers (GOT, GPT and LDH) during the period of ischemia or ischemia-reperfusion. In addition, levels of cytochrome p-450 and NADPH cyt. c reductase activity decreased in proportion to the decrease in microsomal proteins during ischemia or ischemia-reperfusion. On the other hand, superoxide dismutase in blood was significantly increased by ischemia-reperfusion. Rats died within 2 days after liver ischemia of 90 min, while all animals subjected to 30-min ischemia survived. Histopathological examinations indicated that extensive coagulation with erythrocytes occurred and the extent was dependent on the time of ischemia. The liver injury by ischemia-reperfusion could be a useful experimental model for studying liver injury induced by free radicals, for developing hepatoprotective drugs, or for investigating liver transplantation.
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PMID:[An injury of the liver caused by ischemia-reperfusion in rat liver]. 190 28

Recently, the prototype of a novel class of calcium-independent plasmalogen-selective phospholipase A2 activities was identified in the cytosolic fraction of canine myocardium (Wolf, R.A., and Gross, R.W. (1985) J. Biol. Chem. 260, 7295-7303) and subsequently purified and characterized (Hazen, S.L., Stuppy, R.J., and Gross, R.W. (1990) J. Biol. Chem. 265, 10622-10630). We now demonstrate that 15 min of myocardial ischemia utilizing a rabbit Langendorf perfused heart model results in a 10-fold increase in membrane-associated calcium-independent phospholipase A2 activity whose detection is entirely dependent upon utilization of plasmalogen substrate. Ischemia-induced phospholipase activity was identified as a membrane bound member of this class of phospholipases A2 by demonstration of: 1) concomitant production of lysoplasmenylcholine and sn-2 fatty acid from plasmenylcholine substrate; 2) maximal enzymatic activity in the absence of calcium ion; and 3) a 16-fold higher maximum reaction velocity utilizing plasmenylcholine compared to phosphatidylcholine substrate at multiple surface concentrations. Ischemia-induced phospholipase A2 activity was specifically localized to the microsomal fraction and could not be solubilized by sonication, salt treatment, exposure to chelators, or utilization of submicellar concentrations of detergent. The appearance of microsomal phospholipase A2 activity did not require ischemia-induced transcription or translation since identical increases in enzymic activity were obtained in hearts previously treated with actinomycin D and cycloheximide. Collectively, these results demonstrate that a membrane-associated calcium-independent phospholipase A2 that selectively hydrolyzes plasmalogen molecular species is the likely enzymic mediator of accelerated phospholipid catabolism during early myocardial ischemia.
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PMID:Activation of a membrane-associated phospholipase A2 during rabbit myocardial ischemia which is highly selective for plasmalogen substrate. 200 3

Phospholipase A2 (PLA2) activities in cytosolic, mitochondrial, and microsomal fractions of rat kidneys were characterized under control conditions, after ischemia, and subsequent to ischemia and reperfusion. Two forms of PLA2 activity were present in the cytosolic fraction: a high molecular weight form, active against phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which upon purification has a molecular mass of 110 kD; and smaller form (Mr approximately 14 kD), active against PE. In mitochondrial and microsomal fractions a single form (Mr approximately 14 kD), active against both PC and PE, was dominant. Activities in each fraction were optimal at pH 8.5-9.5. Cytosolic PLA2 activity was enhanced when Ca2+ concentration [( Ca2+]) was increased over the range of 10(-7) to 10(-6) M. Mitochondrial PLA2 activity required higher [Ca2+] for activation (greater than 10(-6) M). After 45 min of ischemia cytosolic PLA2 activity was decreased, whereas mitochondrial and microsomal activities were increased. When ischemia was followed by 1 h of reperfusion, cytosolic, mitochondrial, and microsomal activities were enhanced. Ischemia alone did not change the gel filtration chromatography patterns of PLA2 activity, but ischemia and reperfusion resulted in the appearance of a new peak of activity in cytosolic and mitochondrial fractions (Mr approximately 2-3 kD). Thus, the rat kidney has multiple forms of PLA2 activity, likely representing distinct enzymes, with Ca2+ dependencies suggesting regulation by Ca2+ in vivo. Ischemia and reperfusion result in stable increases of PLA2 activity in each subcellular fraction, perhaps related to covalent modifications of PLA2's, which likely account for membrane phospholipid degradation, and increased tissue levels of unsaturated free fatty acids.
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PMID:Subcellular characteristics of phospholipase A2 activity in the rat kidney. Enhanced cytosolic, mitochondrial, and microsomal phospholipase A2 enzymatic activity after renal ischemia and reperfusion. 202 47

Brain phospholipase A2 (PLA2) activity has not been well characterized. Given the importance of this enzymatic activity for a variety of cellular functions in the brain, we characterized the subcellular distribution of PLA2 activity in gerbil brain and evaluated how PLA2 activity was altered by ischemia and reperfusion. Cytosolic, mitochondrial, and microsomal fractions were prepared by differential centrifugation of forebrain homogenates. PLA2 activities of each fraction were assayed by measuring release of arachidonic acid (AA) from exogenous 14C-AA-phosphatidylcholine (PC), -phosphatidylethanolamine (PE), and -phosphatidylinositol (PI). Two forms of PLA2 were present in the cytosolic fraction: a high-molecular-weight form, active against PC and PE, and a smaller form with an Mr of approximately 14 kDa, active against PE. In the mitochondrial and microsomal fractions, a single form (Mr approximately 14 kDa) was dominant, active against both PC and PE. The role of PLA2 activation in ischemic brain injury remains controversial. PLA2 enzymatic activity was characterized in gerbil brain after 10 min of common carotid occlusion, followed by 10 min of reperfusion. Ischemic/reperfused brains had significantly higher PLA2 specific activities in each subcellular fraction. Ischemia and reperfusion did not change the gel-filtration elution patterns of PLA2 activity of the various forms of the enzyme. Cytosolic, mitochondrial, and microsomal activities were optimal at a pH of approximately 8.5. Cytosolic PLA2 activity was enhanced when Ca2+ concentration [( Ca2+]) was increased over the physiological range (10(-7) to 10(-6) M). Mitochondrial and microsomal PLA2 activities were also [Ca2+] dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of phospholipase A2 (PLA2) activity in gerbil brain: enhanced activities of cytosolic, mitochondrial, and microsomal forms after ischemia and reperfusion. 204 88

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
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PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63

A proposed mechanism for irreversible ischemic liver damage has been peroxidation of membrane phospholipids by free radicals. However, the hepatocyte is laden with enzymes which are antioxidants and, therefore, ought to be relatively resistant to oxidative injury. To test the hypothesis that free radical damage from ischemia and reperfusion of the liver is a nonparenchymal cell process, we studied an in vivo model of ischemia. A point of transition from reversible to irreversible ischemia was defined at greater than or equal to 60 min of total ischemia by serial measurements of ATP at control, end of ischemia, and end of reperfusion periods (n = 6 each). Nonparenchymal cells were separated out of 10 livers in each ischemic group using a Percoll gradient. Second derivative spectroscopy did not detect conjugated dienes in any hepatocellular fraction, total cellular, mitochondrial, or microsomal, but did in the nonparenchymal cell fractions of livers from the 60- and 90-min ischemia groups. This in vivo study shows that irreversible ischemia in the rat liver is associated with free radical lipid peroxidation, but that the nonparenchymal cells rather than hepatocytes are the focus of this injury.
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PMID:Lipid peroxidation is a nonparenchymal cell event with reperfusion after prolonged liver ischemia. 235 89

Inhibition of an increase in total content of unsaturated fatty acids in microsomal lipids induced by phenobarbital, alterations of parameters of the fluorescent probe 1,8-ANS-binding with membranes as well as restrictions in induction of liver microsomal monooxygenase enzymatic system were detected during postischemic period after total liver tissue ischemia. Preadministration of alpha-tocopherol and lidocaine prevented distinctly the structure-functional alterations induced by phenobarbital in liver microsomal membranes during postischemic period. Possible factors responsible for limitations of the phenobarbital inducing effect during postischemic period are discussed.
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PMID:[The effect of alpha-tocopherol and lidocaine on the structural-functional rearrangement of liver endoplasmic reticulum membranes after induction with phenobarbital in the postischemic period]. 236 49


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