Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003129 (Anoxia)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of fructose on the intracellular ionic changes evoked by anoxia were studied in freshly isolated rat hepatocytes maintained in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB). Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular sodium (Na+i) with sodium-binding benzofuran isophthalate, intracellular pH (pHi) with 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein, lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate, and viability by trypan blue exclusion. ATP, Pi, phosphomonoesters, and the cell phosphorylation potential assessed by the reciprocal of the Pi/ATP ratio were measured by 31P NMR spectroscopy in real time. Intracellular free Mg2+ (Mg2+i) was calculated from the chemical shift of beta-ATP relative to alpha-ATP in the NMR spectra. Anoxia was induced by perfusing the cells with KHB saturated with 95% N2, 5% CO2. When the perfusate contained 5 mM glucose as substrate, anoxia caused a fall in ATP, a rise in Pi, and in the Pi/ATP ratio, a biphasic increase in Ca2+i that reached 1.45 +/- 0.42 microM and a 6-fold increase in LDH. When 15 mM fructose was used as substrate during the anoxic period, intracellular ATP decreased much faster than with glucose, Pi did not increase, and the concentration of phosphomonoesters increased 2.5-fold. During the first hour of anoxia, the Pi/ATP ratio was higher in the fructose than in the glucose group indicating that the hepatocyte phosphorylation potential and ATP decreased faster and to lower levels with fructose than with glucose. On the other hand, ATP and the phosphorylation potential of the fructose group increased during the second hour of anoxia, in contrast to their continuous decline in the glucose group. The major surge in Ca2+i was depressed 52% when glucose was replaced by fructose: Ca2+i reached only 0.7 +/- 0.2 microM instead of 1.45 +/- 0.42 microM (p less than 0.01). Anoxia also caused an increase in Na+i and an intracellular acidosis. The rise in Na+i was significantly greater with fructose than with glucose. Na+i rose from a control value of 15.9 +/- 2.4 to 32.2 +/- 0.4 mM with glucose and to 48.7 +/- 0.7 mM with fructose (p less than 0.001). The decrease in pHi from a control value of 7.43 +/- 0.03 was consistently greater and faster with fructose than with glucose: 6.59 +/- 0.03 and 7.04 +/- 0.01, respectively. At the same time, fructose completely suppressed LDH release and reduced the loss of viability produced by anoxia from 27.7 +/- 2.9 to 14 +/- 3.1% (p less than 0.05).
 ...
PMID:Fructose protects rat hepatocytes from anoxic injury. Effect on intracellular ATP, Ca2+i, Mg2+i, Na+i, and pHi. 155 92

The effects of anoxia were studied in freshly isolated rat hepatocytes maintained in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB). Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular sodium (Na+i) with SBFI, intracellular pH (pHi) with BCECF, lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate, ATP by 31P NMR spectroscopy in real time, and intracellular free Mg2+ (Mg2+i) from the chemical shift of beta-ATP relative to alpha-ATP in the NMR spectra. Anoxia was induced by perfusing the cells with KHB saturated with 95% N2, 5% CO2. After 1 h of anoxia, beta-ATP fell 66%, and 85% after 2 h, while the Pi/ATP ratio increased 10-fold from 2.75 to 28.3. Under control conditions, the resting cytosolic free calcium was 127 +/- 6 nM. Anoxia increased Ca2+i in two distinct phases: a first rise occurred within 15 min and reached a mean value of 389 +/- 35 nM (p less than 0.001). A second peak reached a maximum value of 1.45 +/- 0.12 microM (p less than 0.001) after 1 h. During the first hour of anoxia, Na+i increased from 15.9 +/- 2.4 mM to 32.2 +/- 1.2 mM (p less than 0.001), Mg2+i doubled from 0.51 +/- 0.05 to 1.12 +/- 0.01 mM (p less than 0.001), and pHi decreased from 7.41 +/- 0.03 to 7.06 +/- 0.1 (p less than 0.001). LDH release doubled during the first hour and increased 6-fold during the second hour of anoxia. Upon reoxygenation, ATP, Ca2+i, Mg2+i, Na+i, and LDH returned near the control levels within 45 min. To determine whether the increased LDH release was related to the rise in Ca2+i, and whether the increased Ca2+i was caused by Ca2+ influx, the cells were perfused with Ca(2+)-free KHB (+ 0.1 mM EGTA) during the anoxic period. After 2 h of anoxia in Ca(2+)-free medium, beta-ATP again fell 90%, but Ca2+i, after the first initial peak, fell below control levels, and LDH release increased only 2.7-fold. During reoxygenation, Ca2+i, ATP, Na+i, and LDH returned near the control levels within 45 min. These results suggest that the rise in Ca2+i induced by anoxia is caused by an influx of Ca2+ from the extracellular fluid, and that LDH release and cell injury may be related to the resulting rise in Ca2+i.
 ...
PMID:Effect of anoxia on intracellular ATP, Na+i, Ca2+i, Mg2+i, and cytotoxicity in rat hepatocytes. 163 81

Proximal tubules of the S1, S2 and S3 segments, medullary thick ascending limbs of Henle's loop (MAL) and cortical collecting tubules (CCT) were individually microdissected from rabbit kidneys and cultured for seven days in hormonally defined media. Anoxia was induced by incubation of cultures in normal medium for 45 min at 25 degrees C in an atmosphere of nitrogen (N2), and cell death was measured by nigrosine dye uptake. Immediately after anoxia, cell death was highest in S3 and MAL segments greater than S2 greater than S1 = CCT. The combined effects of anoxia and substrate (glucose, vitamins, amino acid) omission determined after incubation of cultures in phosphate buffered saline containing Ca2+ and Mg2+ (PBS) for 45 min in N2 also showed differential killing dependent on segment of origin: MAL greater than S3 greater than S2 CCT greater than S1. The effects of in vitro "reflow" were tested by returning cells to their normal oxygenated culture media at 37 degrees C. After the 45 min of anoxia and four to six hr of reflow in normal calcium-containing media, all cells from each segment were dead. Reflow in media lacking calcium for two hr immediately after anoxia then followed by return to normal calcium-containing media was associated with the survival of a significant percentage of cells for 48 hr: S1 (35.3 +/- 2.0%), S2 (30.0 +/- 2.0%), S3 (46.2 +/- 3.0%), MAL (38.7 +/- 3.0%), CCT (28.2 +/- 2.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nephron segment and calcium as determinants of anoxic cell death in renal cultures. 374 34

The Mongolian gerbil displays spontaneous seizures and is used as a model for global ischemia. This study investigated the electrophysiological events associated with 0-Mg(2+)-induced seizures in gerbil hippocampal slices. In the rat hippocampal slice, 0-Mg2+ medium leads to rapid extracellular epileptic depolarization (ED) accompanied by long-term synaptic failure. Both evoked and spontaneous epileptiform activity was observed in the gerbil hippocampal slice after the introduction of the 0-Mg2+ aCSF. However, unlike the rat, ED was rarely observed in the gerbil hippocampal slice (2/17). When ED occurred, synaptic responses recovered (75%) within 20 min. This resistance to epileptic depolarization did not generalize to experimental ischemia-induced depolarization. Anoxia in 2 mM D-glucose produced anoxic depolarization in all gerbil hippocampal slices tested (6/6).
 ...
PMID:Resistance to epileptic, but not anoxic, depolarization in the gerbil hippocampal slice preparation. 802 97

We evaluated the effects of magnesium on extracellular dopamine (DA) and its metabolites in the striatum of 5-d-old rats submitted to 16 min of anoxia using microdialysis and HPLC. Rat pups were divided into three groups and received either 1) intrastriatal perfusion (IS) of MgSO4, 2) intraperitoneal injection (IP) of MgSO4, and 3) NaCl and Ringer's solution, respectively in place of MgSO4. After stabilization, Mg2+, saline, and Ringer's solution were administered; then, 114 animals were exposed to 100% nitrogen for 16 min. Anoxia induced a DA surge, an acutely marked increase of DA, in both the control and the IP group. In contrast, the DA surge was significantly suppressed in the IS group (p < 0.01, analysis of variance). During anoxia, the plasma Mg2+ in the IP group, but not in the IS group, maintained a significantly higher level compared with the basal level. On the other hand, Mg2+ in the perfusates in the IS group, but not in the IP group, maintained a significantly high level during anoxia. Alterations induced by anoxia in other metabolites, 3,4-dihydroxyphenylacetic acid, homovanillic acid, norepinephrine, and 5-hydroxyindole-3-acetic acid, did not significantly differ among the three groups. We propose that elevated levels of Mg2+ in the striatum had inhibitory effects on the DA surge during anoxia.
 ...
PMID:Magnesium attenuates a striatal dopamine increase induced by anoxia in the neonatal rat brain: an in vivo microdialysis study. 916 93

It is important to monitor mitochondrial conditions, and light scattering (LS) measurements have been applied to the detection of morphological changes in mitochondria in vivo. Little is known about the morphological and LS responses of brain mitochondria to oxygen withdrawal, a critical factor in cell death. We have therefore investigated the morphological and LS responses of isolated brain mitochondria to anoxia. Anoxia induced an increase in LS, reflecting mitochondrial matrix shrinkage. This response was reversible, but was reduced by adding digitonin, which disrupted the outer membrane selectively. This suggested that integrity of the outer membrane was necessary for the matrix response. We further examined the effects of Mg2+ and ATP on the responses because both exist in cells and modulate the changes in matrix volume. Although Mg2+ and ATP reduced the rates of increase and decrease in LS, respectively, the magnitudes of the increases in LS caused by anoxia stayed at over 80% of the control level (no Mg2+) in the presence of Mg2+ and ATP. This suggested that the increase in LS occurred in cells containing Mg2+ and ATP during anoxia. In contrast, that caused by inhibitors of the electron transport chain was reduced to below 30% of the control level in the presence of Mg2+. The present in vitro study provides a basis for interpretation of LS signals from mitochondria in brain research during oxygen withdrawal.
 ...
PMID:Anoxia induces matrix shrinkage accompanied by an increase in light scattering in isolated brain mitochondria. 1474 19

Anoxia can lead to skeletal muscle damage. In this study we have investigated whether an increased influx of Ca2+, which is known to cause damage during electrical stimulation, is a causative factor in anoxia-induced muscle damage. Isolated extensor digitorum longus (EDL) muscles from 4-week-old Wistar rats were mounted at resting length and were either resting or stimulated (30 min, 40 Hz, 10 s on, 30 s off) in the presence of standard oxygenation (95% O2, 5% CO2), anoxia (95% N2, 5% CO2) or varying degrees of reduced oxygenation. At varying extracellular Ca2+ concentrations ([Ca2+]o), 45Ca influx and total cellular Ca2+ content were measured and the release of lactic acid dehydrogenase (LDH) was determined as an indicator of cell membrane leakage. In resting muscles, incubated at 1.3 mM Ca2+, 15-75 min of exposure to anoxia increased 45Ca influx by 46-129% (P<0.001) and Ca2+ content by 20-50% (P<0.001). Mg2+ (11.2 mM) reduced the anoxia-induced increase in 45Ca influx by 43% (P<0.001). In muscles incubated at 20 and 5% O2, 45Ca influx was also stimulated (P<0.001). Increasing [Ca2+]o to 5 mM induced a progressive increase in both 45Ca uptake and LDH release in resting anoxic muscles. When electrical stimulation was applied during anoxia, Ca2+ content and LDH release increased markedly and showed a significant correlation (r2=0.55, P<0.001). In conclusion, anoxia or incubation at 20 or 5% O2 leads to an increased influx of 45Ca. This is associated with a loss of cell membrane integrity, possibly initiated by Ca2+. The loss of cell membrane integrity further increases Ca2+ influx, which may elicit a self-amplifying process of cell membrane leakage.
 ...
PMID:Anoxia induces Ca2+ influx and loss of cell membrane integrity in rat extensor digitorum longus muscle. 1590 8