The role of glycolysis in the protective effect of amtizol during acute hypoxia

In rats, protective effect of amtizol was found to depend on the rate of carbohydrate substrate in the organism as well as on the glycolysis activity. Amtizol was able to activate utilising of carbohydrates in a glycolytic way in satisfied rats with a blockade of glycolysis by monoiodacetate, whereas glyconeogenesis was activated in starving rats.     

The protective effect of carnosine in hypoxia and reoxygenation of the isolated rat heart]

The effect of carnosine (15 mM) on the contractile activity of isolated rat hearts contracting in an isotonic regime (37 degrees C at a 5 Hz stimulation frequency) has been studied. Carnosine added to the perfusing solution had no effect on the contractile activity either in hypoxia or during reoxygenation but decreased it with a simultaneous increase in the coronary flow during reoxygenation. Carnosine inhibited by 60% the lactate dehydrogenase release from cardiac cells. A conclusion is drawn that the protective effect of carnosine is due to its membrane-stabilizing action which is implemented during inhibition of peroxidation of membrane lipids.     

The significance of the mu- and delta-opiate receptors in realizing enkephalin action on the course of hypoxic hypoxia]

New enkephalins analogues have been synthesized. They are characterized by linear, cyclic and branched peptide chain. A relationship has been established between antihypoxic activity of opioid peptides an their interaction with opiate receptors. Compounds efficiently interacting with mu-receptors irrespective of delta-receptors affinity, promote longer survival of mice in hypoxia. The antihypoxic effect of opioids is proportional to their specificity to mu-receptors.     

The protective role of estradiol under extreme conditions]

It has been demonstrated that estradiol increases the resistance of the animals to hemorrhagic shock. Apparently, it is accounted for by its positive effect on cardiovascular system (by stimulation of myocardial contractility, stabilization of ATP and CF pools, inhibition of lipid peroxidation and lysosomal enzymes, etc.).     

The role of malate dehydrogenase in adaptation to hypoxia in invertebrates]

In muscle tissue of lamellibranch molluscs and crustaceans (cf. Table for the species studied), high levels of malate dehydrogenase and low ones of lactade dehydrogenase were detected. There is a direct relationship between the value of MDH/LDH ratio and the capacity of organisms to withstand temporary anaerobiosis. Animals with high ratio may adapt to hypoxia by transition from aerobic metabolism to anaerobic one.     

Do anticonvulsant drugs exert protective effect against hypoxia?

The effect of anticonvulsants was studied on survival time in mice subjected to hypoxia either by decompression or by prolonged asphyxia. Except trimethadione all the compounds tested enhanced survival time. These results suggest that the protective effect observed might be due directly to the inhibition of hypoxic convulsive seizures.     

The role of hypoxia in the effect of glucose load on irradiated tumor cells

In experiments on Ehrlich ascites tumor cells it was shown that hypoxia, which reduces the lethal effect of gamma-rays, can considerably enhance the injury of cells by glucose. Treatment of tumor cells with glucose in hypoxic conditions followed by exposure to ionizing radiation under both hypoxia and normal aeration causes a 6-7-fold increase in cell injury as compared to irradiation alone. Moreover, the glucose treatment in hypoxic conditions (without concomitant irradiation) may cause approximately 99% death of tumor cells. The data obtained permit to consider the glucose treatment as an effective means by breaking the tumor radioresistance conditioned by a pool of hypoxic cells.     

Evaluation by electrocorticogram of the protective action of piridoxilate against cerebral hypoxia in rats]

Piridoxilate, at the concentration of 120 mg/kg i.p. in rats, enhanced resistance of these animals to hypoxia (N2 : O2 3,2 %). The electrocorticogram (ECOG) is used to indicate the effectiveness of the drug in lowering the time of electrographic silence, on control (n=19) and pretreated rats (n=12). The ECOG was recorded also during the recovery period under pure oxygen. In pretreated rats, the ECOG records became flat in approximately 551 sec (versus 269 sec on the control group). The latent period of successive steps of cerebral anoxia were delayed in pretreated rats exposed to hypoxia. During the recovery period, piridoxilate seems to enhance the restoration of normal ECOG, as a function of the duration of hypoxia.     

Protective effect of malonic acid in hypoxic hypoxia]

Malonic acid injection causes an increase in the survival of rats with acute hypoxic hypoxia. Endogenic malonic acid is supposed to be of great importance in stimulating tissue resistance to hypoxia.     

The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia

Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood–brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK.     

Conditions,necessary for realizing the catalytic effect of enzymes: role of the environment

A hypothesis of enzymic catalysis was put forward according to which the energy of the exothermic reaction that takes place in aqueous medium is used for a shift of equilibrium in the endothermic reaction, a reaction involving hydrated ions. This occurs in accordance with the Le Chatelier's principle, and, as a result of water dissociation in a homogeneous medium, a gradient of H+ and OH- ions is generated at the water/protein interface. It follows from the hypothesis that the chemical conversion of the substrate to the product is preceded by the attack of hydrated ions on the protein and their association on the protein (attack of the nucleophilic agent followed by the acception of the proton). This results in the formation of a cyclic peroxide in the amino acid residue and a C=O-->[C=O]* transition. The return of the carbonyl to the ground state makes it possible to store a part of free energy and use it for converting the enzyme to a state with a higher conformational energy. Thus, we consider the electron excited state in the protein as a state necessary for dark reactions. This implies that, in addition to the effect of sorption of substrate on protein, another aspect of behavior of the dynamic system should be taken into account. All factors producing a real effect on the internal protein dynamics are important for the conformational transition and enzymic reaction as a whole, and the rate constant should be determined with allowance for these factors.     

The possible protective effect of cysteine during acute alcohol intoxication]

In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.     

The role of calcium ions in the molecular mechanism of the protective mechanism of exogenous phosphocreatine]

The role of Ca2+ in the manifestation of the cardioprotective effect of phosphocreatine (PCr) on the ischemic myocardium was studied in isolated rat hearts perfused by the Langendorf method. Under ischemic cardiac arrest induced by a Ca(2+)-free perfusing solution PCr had no protective effect on the ischemic myocardium. PCr accelerated the postischemic restoration of contractility of hearts perfused with a solution containing 0.5 and 1.2 mM Ca2+. The structural analog of PCr, phosphoarginine, possessing a Ca(2+)-binding capacity similar to that of PCr, had no protective effect. The effects of PCr and Ca2+ on the package of sarcolemmal vesiculate lipids were studied by ESR spectroscopy. PCr induced a more dense package of membrane phospholipids at weakly acidic and neutral values of pH (but not at pH 8.5). Although at pH 5.5 Ca2+ did not affect the membrane structure, it potentiated the effect of PCr on sarcolemmal phospholipids. Thus, the protective effect of PCr on the ischemic myocardium is not linked with its ability to bind Ca2+; however, Ca2+ is an indispensable component of the mechanism underlying the protective effect of PCr on the ischemic myocardium.     

The effect of hypoxia on the branchial vascular system of the perfused trout head]

Measurements of inflow (VE) and arterial (Vsa) and venous (VSv) outflow in trout perfused head preparations show significant decreases of VE and VSa during low PO2 saline perfusion (20 torr). Comparable results are gained during adenosine perfusion (1.10(-8) to (1.10(-6) M). Theophylline (10(-4) M) inhibits both hypoxia and adenosine effects.     

Mechanism of the protective effect of adaptation to hypoxia on the development of allergic arthritis

It has been established that adaptation of Wistar rats to high-altitude hypoxia led to a reduction of inflammatory lesions occurring in adjuvant arthritis. It has been shown that the mechanisms associated with a decrease in the content of mediators (serotonin, histamine) of the chemical and pathophysiological stages of allergic reactions formation in the adapted animals underlie the protective effect of adaptation. Adaptation to hypoxia appreciably lowered the sensitivity of the sensitized rats to serotonin.     

The effect of hypoxia in development

There is increasing evidence that the oxygen supply to the human embryo in the first trimester is tightly controlled, suggesting that too much oxygen may interfere with development. The use of hypoxia probes in mammalian embryos during the organogenic period indicates that the embryo is normally in a state of partial hypoxia, and this may be essential to control cardiovascular development, perhaps under the control of hypoxia-inducible factor (HIF). A consequence of this state of partial hypoxia is that disturbances in the oxygen supply can more easily lead to a damaging degree of hypoxia. Experimental mammalian embryos show a surprising degree of resilience to hypoxia, with many organogenic stage embryos able to survive 30-60 min of anoxia. However, in some embryos this degree of hypoxia causes abnormal development, particularly transverse limb reduction defects. These abnormalities are preceded by hemorrhage/edema and tissue necrosis. Other parts of the embryo are also susceptible to this hypoxia-induced damage and include the genital tubercle, the developing nose, the tail, and the central nervous system. Other frequently observed defects in animal models of prenatal hypoxia include cleft lip, maxillary hypoplasia, and heart defects. Animal studies indicate that hypoxic episodes in the first trimester of human pregnancy could occur by temporary constriction of the uterine arteries. This could be a consequence of exposure to cocaine, misoprostol, or severe shock, and there is evidence that these exposures have resulted in hypoxia-related malformations in the human. Exposure to drugs that block the potassium current (IKr) can cause severe slowing and arrhythmia of the mammalian embryonic heart and consequently hypoxia in the embryo. These drugs are highly teratogenic in experimental animals. There is evidence that drugs with IKr blockade as a side effect, for example phenytoin, may cause birth defects in the human by causing periods of embryonic hypoxia. The strongest evidence of hypoxia causing birth defects in the human comes from studies of fetuses lacking hemoglobin (Hb) F. These fetuses are thought to be hypoxic from about the middle of the first trimester and show a range of birth defects, particularly transverse limb reduction defects.     

The effect of hypoxic hypoxia on the physicochemical and functional properties of hemoglobin in rats]

The effect of intermittent altitude chamber hypoxia is established to cause an increase in solvability of laboratory rat hemoglobin. Results of immunochemical and fluorescent analysis of the samples of hemoglobin and its component are presented and discussed. They prove that changes in solvability of hemoglobin are determined by the conformational reconstructions of the respiration protein as a result of formation of the complexes with internally erythrocytic metabolites.