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

Lipid peroxidation disrupts membrane integrity and causes structural and functional alterations in ischemic tissues. Taurine and ketamine are putative ischemic protectants that affect Ca2+ influx. Here we report the influence of these compounds on lipid peroxidation in subcellular fractions, isolated cells and intact tissue from bovine retinas. P2 membrane fractions and isolated cells were exposed to the lipid peroxidation inducers cadmium chloride (200 microM) or L-ascorbic acid (1 mM) in the presence of 0-50 mM taurine, 0-10 mM ketamine, 1 mM kynurenic acid or 1 mM dextromethorphan. The latter compounds are N-methyl-D-aspartate receptor antagonists. Lipid peroxidation in isolated eyes reperfused after 1 h of ischemia either with or without protectants was determined by thiobarbituric acid assay. Glutathione was measured in isolated retinas subjected in vitro to simulated ischemia (no glucose or oxygenation) for 60 min either alone or in the presence of taurine or ketamine. Ketamine inhibited chemical- or ischemia-induced lipid peroxidation as well as ischemic glutathione depletion. Under the same conditions, taurine failed to affect lipid peroxidation or glutathione. The data show a direct effect of ketamine on lipid peroxidation and point to separate mechanisms of action for ketamine and taurine.
 ...
PMID:Effects of taurine and ketamine on bovine retinal membrane lipid peroxidation. 183 70

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on striatal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right striatum of postnatal day 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and the animals were exposed to 8% oxygen for 2.5 hours (n = 22). Rats exposed to ligation alone (n = 10) or hypoxia alone (n = 8) and untreated controls (n = 17) were also studied. Two hours after probe insertion, a 30-minute baseline microdialysis sample was obtained. After arterial ligation, two additional baseline samples were collected. Five more samples were collected over the next 2.5 hours (in 8% oxygen or room air). Eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected in dialysates using a high-performance liquid chromatography assay with electrochemical detection. In untreated controls, amino acid efflux did not change over 4 hours. During hypoxia-ischemia, efflux values fluctuated widely, with marked intra-animal and interanimal variability. Efflux peaks for each amino acid were defined as values greater than the highest control mean value plus two standard deviations. Glutamate efflux peaks (greater than 7 pmol/min compared with 2 pmol/min at baseline) were detected in no controls and in eight hypoxic-ischemic rats (p = 0.006, Fisher's two-tailed exact test). Taurine efflux peaks (greater than 75 pmol/min compared with 10 pmol/min for controls at baseline) were detected in 10 hypoxic-ischemic rats and one control (p = 0.01) and in seven of the eight animals in which glutamate efflux peaks occurred (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of perinatal stroke on striatal amino acid efflux in rats studied with in vivo microdialysis. 185 13

The loss of mechanical function in rat hearts subjected to either the calcium-paradox or global ischemia heart failure models was found to correlate with decreases in myocardial taurine levels. Therefore, the effect of taurine treatment was assessed in the two failure procedures. The presence of taurine protected against loss of mechanical function resulting from the calcium paradox and prevented both the large decline in sarcolemmal ATPase activities and the increase in sarcolemmal calcium binding normally associated with this model. Parallel studies on reperfused, taurine-untreated ischemic hearts showed only minor changes in these sarcolemmal functions. Taurine treatment normalized the slight increase in calcium binding associated with ischemia, but had no observable effect on recovery of mechanical function. Although taurine returns selected parameters of the sarcolemma toward normal in both models, it only improves mechanical function in the paradox model. This suggests that calcium paradox-induced heart failure is more closely associated with sarcolemmal dysfunction than ischemic heart failure.
 ...
PMID:Effect of taurine on calcium paradox and ischemic heart failure. 645 Nov 84

In the present study, spontaneous and evoked release of selected amino acids in the rat spinal cord was studied using in vivo microdialysis. Perfusion of the microdialysis probe with 100 K+ evoked a 2-4-fold increase in release of the putative neurotransmitters aspartate, glutamate and taurine while glutamine was decreased. K(+)-evoked release of glutamate was almost completely Ca(2+)-dependent while that of aspartate was partially Ca(2+)-dependent. Taurine release was not affected by substituting Ca2+ with Co2+. Perfusion with 5 mM N-methyl-D-aspartate (NMDA) evoked 3-9-fold release of glutamate, glycine and taurine and a small increase in extracellular beta-alanine. No significant changes in glutamine and serine were found. 5 mM of the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced NMDA-evoked release of glutamate and taurine by approx. 50%. 5 mM 3-amino-1-hydroxypyrrolid-2-one (HA-966), an agonist at the glycine site of the NMDA receptor with very low efficacy, completely inhibited NMDA-evoked release of taurine and reduced the levels of released glutamate below baseline, similar to the effect of 1 mM CPP alone. The present results show that in situations of excessive release of excitatory amino acids such as spinal ischemia and trauma. NMDA receptor-evoked release of glutamate may amplify the deleterious process and spread the damage.
 ...
PMID:In vivo studies on NMDA-evoked release of amino acids in the rat spinal cord. 758 Aug 74

Deficiency of the amino acid taurine is implicated in various pathologic states of the heart. Besides other effects, taurine has been proposed to be an antioxidant. However, its benefit under conditions associated with the generation of reactive oxygen species in the heart has not been clearly demonstrated. To assess the potential of taurine to influence neutrophil-dependent reperfusion injury, a model was developed based on the isolated working guinea pig heart. After an initial work phase, hearts were subjected to 15 min of global ischemia. Reperfusion, in a nonworking mode, was carried out in the absence or presence of homologous neutrophils (PMN) and/or taurine. After 15 min, work was resumed and percentage recovery of function was determined another 20 min later. During the reperfusion phase, coronary venous effluent was collected to quantify release of lactate and glutathione, markers of ischemic challenge and redox-stress, respectively. Furthermore, direct effects of taurine on radical formation were investigated in a chemiluminescence assay. Control hearts without application of PMN or taurine had a postischemic recovery of external heart work (EHW) of 76%, in the presence of taurine (15 mM) recovery was 72%. The application of PMN for merely the first minute of reperfusion led to a significant decrease in recovery to 30%, PMN having no effect without a foregoing ischemia. When taurine was additionally applied during reperfusion, EHW recovered to 60%. Release of lactate and of oxidized glutathione (GSSG) did not differ between the groups. In contrast, effluent concentrations of reduced glutathione (GSH) were considerably elevated by the presence of PMN in the sample and remained high even after PMN-washout. Taurine tended to attenuate this PMN effect. At the 5th and 10th min of reperfusion, GSH release of individual hearts correlated inversely with postischemic recovery of EHW. Surprisingly, taurine, by itself, did not significantly alter glutathione release. However, taurine (15 mM) markedly reduced luminol-dependent chemiluminescence elicited by activated guinea pig PMN as well as by chemically generated hypochlorous acid and hydroxyl radicals, but not superoxide radicals. Our results demonstrate that taurine protects the heart from PMN-induced reperfusion injury and oxidative stress. Because respiratory burst activity of PMN was also significantly reduced in the presence of taurine, the beneficial effect appears to be mediated by antioxidative properties of taurine.
 ...
PMID:Taurine protects the heart from neutrophil-induced reperfusion injury. 759 Mar 95

Taurine (2-aminoethane sulfonic acid) is a physiologic amino acid involved in cellular osmoregulation in various species including man. This study was intended to compare the respective effects of cold storage and consecutive ischemic rewarming of the liver postischemic hepatic flow and hepatocellular outcome upon reperfusion with or without the addition of taurine to the preservation medium. Livers from male Wistar rats were rinsed free of blood via the portal vein and stored ischemically at 4 degrees C in UW solution. Livers from group 1 were then rinsed again with 10 ml Ringer's solution and reperfused with Krebs-Henseleit buffer at a constant pressure of 10 mmHg for 45 min at 37 degrees C in a nonrecirculating manner. Livers from groups 2 and 3 were subjected to 30 min of warm ischemia subsequent to cold storage and prior to reperfusion with 10 mM taurine added to the UW solution in group 3. While there were only very few signs of hepatic injury in group 1, the additional period of warm ischemia (group 2) led to a significant reduction in early perfusate flow and enhanced enzyme leakage from the livers during postischemic rinse and reperfusion. Livers in group 3 exhibited an amelioration in hepatic circulation and significantly reduced enzyme release as compared to group 2. The results clearly demonstrate a remarkable impact of postischemic rewarming on graft viability. Furthermore, the addition of taurine to the preservation medium was shown to improve hepatic circulation and enhance viability of the liver upon reperfusion.
 ...
PMID:Effects of taurine on liver preservation in UW solution with consecutive ischemic rewarming in the isolated perfused rat liver. 762 75

Little is known about blood to brain taurine transport despite substantial evidence suggesting a role of taurine in brain volume regulation during osmotic stress or conditions inducing cell swelling, such as ischemia. We have made measurements of the taurine influx rate constant (K1) with [3H]taurine in three conditions: raised plasma taurine concentrations induced by infusion with 50 mM taurine (10 microliters/100 g/min); osmotic stress induced by i.p. injections of 1.5 M NaCl (2 ml/100 g) or distilled water (10 ml/100 g); and 4 h of middle cerebral artery occlusion (MCAo). In rats with MCAo, additional determinations were made of tissue water and taurine contents, and blood-brain barrier passive permeability with [3H]alpha-aminoisobutyric acid. Taurine infusion increased plasma taurine from 110 +/- 63 microM (SD) to 407 +/- 63 (p < 0.001) and decreased taurine K1 at the blood-brain barrier by 70% (p < 0.001), signifying saturable uptake that maintained unidirectional influx constant. Similarly, although hypo- and hyperosmolality increased and decreased plasma taurine concentration, respectively, a reciprocal relationship between K1 and plasma taurine in these experiments ensured that unidirectional fluxes of taurine into brain were unchanged by osmotic stress. During MCAo, the taurine K1 was reduced 80% in the ipsilateral ischemic tissue compared with the contralateral nonischemic tissue (p < 0.001). This decline may be due to a release of taurine into the brain circulation, because there was a concomitant loss of tissue taurine of 7.4 +/- 2.4 mmol/g dry weight (p < 0.05). Alternately, if taurine uptake is sodium dependent, the decline might reflect a disruption of the endothelial sodium gradient.
 ...
PMID:Blood-brain barrier taurine transport during osmotic stress and in focal cerebral ischemia. 767 78

Extracellular concentrations of amino acids in halothane-anesthetized rats were measured using a microdialysis fiber inserted transversely through the dorsal spinal cord at the level of the lumbar enlargement in conjunction with HPLC and ultraviolet detection. After a 2-h washout and a 1-h control period, 20 min of reversible spinal cord ischemia was achieved by the inflation of a Fogarty F2 catheter passed through the femoral artery to the descending thoracic aorta. After 2 h of postischemic reperfusion, animals were transcardially perfused with saline followed by 10% formalin or 4% paraformaldehyde. The glutamate concentration in the dialysate was significantly elevated after 10 min of occlusion and returned to near-baseline during the first 30 min of reperfusion. Taurine was elevated significantly 0.5 h postocclusion and continued to increase throughout the 2 h of reperfusion. Glycine concentrations showed a tendency to be slightly above baseline during the reperfusion period. Glutamine concentrations modestly increased following 2 h of reperfusion. No significant changes in aspartate, asparagine, and serine were detected. In control animals no significant changes in any amino acids were detected. To assess the role of complete spinal ischemia on spinal glutamate release, studies were carried out using cardiac arrest. Twenty minutes after induction of cardiac arrest, the glutamate concentration was increased about 350-400%. In a separate group of animals, spinal cord blood flow (SCBF) and its response to decreased CO2 were measured using a laser probe implanted into the epidural space at the level of the L2 vertebral segment. SCBF decreased to 5-6% of the control during aortic occlusion. After reversible ischemia, marked hyperemia was seen for the first 15 min, followed by hypoperfusion at 60 min. Under control-preischemic conditions a decrease in arterial CO2 content caused a decrease in SCBF of about 25%. This autoregulatory response was almost completely absent when assessed 60 min after a 20-min interval of aortic occlusion. Histopathological analysis of spinal cord tissue from these animals demonstrated heavy neuronal argyrophilia affecting small and medium-sized neurons located predominantly in laminae III-V. These changes corresponded to signs of irreversible damage at the ultrastructural level. Occasionally, small areas of focal necrosis, located in the dorsolateral part of the dorsal horn and anterolateral part of the ventral horn, were found. The results are consistent with a role for glutamate in ischemically induced spinal cord damage and suggest that taurine elevation detected during the early reperfusion period may serve as an important indicator of irreversible spinal cord neuronal damage.
 ...
PMID:Transient spinal ischemia in rat: characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage. 801 7

The putative osmoregulatory agent, taurine, is lost from the brain during hypo-osmotic stress or ischemia, but the regulatory mechanisms involved in this loss have not been fully elucidated. In this study, we have examined taurine transport by the isolated rat choroid plexus, one element of the brain-blood interface, and examined how it may be regulated as part of brain volume regulation. Choroid plexus taurine uptake was Na- and Cl-dependent with a Vmax and Km of 6.5 +/- 0.3 pmol/mg/min and 232 +/- 33 microM. The latter is substantially greater than the normal CSF taurine concentration and this may be important in removing taurine released into the CSF during parenchymal cell swelling. Taurine uptake also appears calmodulin dependent as it was reduced by 84 and 91% in the presence of 25 microM trifluoperazine and 100 microM W-7, two calmodulin inhibitors. Taurine efflux from choroid plexus was stimulated by trifluoperazine, taurine, and hypo-osmotic stress. The latter two effects were reduced by niflumic acid, suggesting that taurine and hypo-osmotic stress act on the same pathway. The stimulation of efflux by hypo-osmotic stress decreased with time, whereas the effect of external taurine was sustained. If this efflux pathway is involved in the movement of taurine from choroid plexus to blood, these results suggest that changes in extracellular taurine may be more important than the direct effect of hypo-osmolality in the long-term loss of taurine from the brain.
 ...
PMID:Choroid plexus taurine transport. 873 18

It has been suggested that oxygen-derived free radicals play an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothesized to exert its protective effect on NSAIDs-induced gastric injury by its antioxidant properties. The protective effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats. Pretreatment with 0.25 or 0.5 g/kg of taurine one day before or for 3 days significantly reduced gastric lesion formation and inhibited the elevation of lipid peroxide level in gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment with indomethacin. Taurine (5-20 mM) inhibited chemiluminescence of neutrophils activated by FMLP. Human neutrophils (polymorphonuclear leukocytes) adhered to the confluent monolayer of human umbilical vein endothelial cells (HUVEC) after coincubation with indomethacin. This neutrophil adhesion induced by indomethacin to HUVEC was prevented by taurine in a dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDs-induced gastric mucosal injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.
 ...
PMID:Protective effect of taurine on indomethacin-induced gastric mucosal injury. 891 52


1 2 3 4 5 6 7 Next >>