Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study focuses on reversible mitochondrial ultrastructural alterations in myocardial myocytes that correspond or accompany reversible metabolic depression observed after oxygen radical exposure. The myocytic mitochondrial membranes and matrix of isolated Langendorff-perfused rat hearts were examined by semiquantitative morphometry using the electron micrograph as unit. The hearts were exposed to either standard perfusion (group A), 10 min of oxygen radicals together with superoxide dismutase and catalase followed by 35 min of recovery (group B), 10 min of oxygen radicals alone (group C), or 10 min of oxygen radicals followed by 35 min of recovery (group D). Mitochondrial ultrastructural alterations were detected in only a few micrographs in groups A and B. The frequency of micrographs with mitochondrial ultrastructural alterations was 69% in group C and 62% in group D. In the group exposed to 10 min of oxygen radicals without recovery (group C) condensed pentalaminar membranous profiles arranged in parallel, interpreted to be closely adhering cristae, were detected in the intracristal compartment of myocytic mitochondria in 50% of the micrographs. The cristal adhesions were associated with other mitochondrial ultrastructural changes. Cristal adhesions were not present in group A or B, and were rarely found in the group exposed to 10 min of oxygen radicals followed by 35 min of recovery (group D). Thus, the cristal adhesions appear to be reversible alterations caused by exposure to oxygen radicals.
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PMID:Reversible ultrastructural alterations in the myocytic mitochondria of isolated rat hearts induced by oxygen radicals. 918 26

Numerous studies argue that salicylic acid (SA) is an important component of the plant signal transduction pathway(s) leading to disease resistance. The discovery that the SA-binding protein is a catalase, whose activity is blocked by SA, led to the proposal that one of SA's modes of action is to inhibit this H2O2-degrading enzyme and thus elevate H2O2 levels. To test this model, an attempt was made to mimic the action of SA by reducing the synthesis of catalase using antisense RNA technology. Analyses of transgenic tobacco plants that expressed the tobacco catalase 1 (cat1) or catalase 2 (cat2) gene in an antisense orientation indicate that there is no correlation between modest to high levels of reduction in catalase activity and activation of plant defenses such as pathogenesis-related (PR)-1 protein synthesis. However, three independent antisense catalase transgenic plants (ASCAT1 Nos 16, 17, and 28), which exhibited the most severe reduction in catalase activity (approximately 90% or more), developed chlorosis or necrosis on some of their lower leaves. These same leaves accumulated very high levels of PR-1 proteins and showed enhanced resistance to tobacco mosaic virus. Necrosis and elevated SA, which appear to result from severe depression of catalase levels, may be responsible for the induction of these defense responses.
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PMID:Development of necrosis and activation of disease resistance in transgenic tobacco plants with severely reduced catalase levels. 919 71

The effects of different doses of insulin (INS) (0.4 or 4.0 IU/kg body mass, i.p., for 3 hr) and 6-hydroxydopamine (6-HDA) (100 mg/kg., i.p.) on the activities of antioxidant enzymes--copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT) and catecholamine degrading enzyme monoamine oxidase (MAO-A)--in the rat interscapular brown adipose tissue (IBAT) were studied. In vivo 6-HDA administration, which induces the destruction of sympathetic nerves, markedly reduced IBAT CuZnSOD activity but did not change MnSOD and CAT activities. However, the low dose of INS, which did not induce hypoglycemia, significantly increased the activity of both IBAT mitochondrial enzymes (MnSOD and MAO-A) of control rats. This INS effect on MnSOD was abolished by 6-HDA. On the contrary, CuZnSOD activity was markedly reduced under the influence of INS in both control and 6-HDA-treated rats, whereas for the maintenance of the control level of this enzyme activity, the intact sympathetic nervous system (SNS) is necessary. INS, independent of the dose applied, did not affect CAT activity in control rats, whereas only low INS dose increased the activity of this enzyme in 6-HDA-treated rats. The results indicate that the stimulatory effect of INS on the IBAT mitochondrial enzymes studied is dose dependent and in the case of MnSOD is mediated by SNS. However, the depression in the activity of CuZnSOD is independent of the above-mentioned factors.
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PMID:Activities of antioxidant enzymes and monoamine oxidase-A in the rat interscapular brown adipose tissue: effects of insulin and 6-hydroxydopamine. 921 19

Acidosis during exercise has long been associated with skeletal muscle fatigue. Recent evidence also has linked reactive oxygen species (ROS) with fatigue in skeletal muscle, including the diaphragm. We hypothesized that acidosis (designed to mimic blood pH during maximal exercise) would worsen ROS-induced depression of diaphragm contractility. The xanthine oxidase (XO) reaction in solution (0.01 U/ml) allows direct assessment of the effects of oxidant stress by ROS. Costal diaphragm fiber bundles from 24 Sprague-Dawley rats (200-250 g) were divided into four treatment groups: 1) pH 7.4, no XO (H); 2) pH 7.4 + XO (HXO); 3) pH 7.0, no XO (L); and 4) pH 7.0 + XO (LXO). Baseline twitch mechanics and force-frequency relationships (Pre) were determined in control Krebs solution (pH 7.4, no XO) before treatment. Treatment solutions were introduced, and the diaphragm underwent 2 min of contractions at 25 Hz (250 ms) at a rate of 1/s. After 10 min of recovery, the control solution was reintroduced into the bath and postcontractile function (Post) was measured. Significant reductions in twitch tension and low-frequency tetanic tension were greater in HXO and LXO compared with H, without an effect on maximal tetanic tension. One-half relaxation time was prolonged only by the combination of acidosis and oxidative stress. Addition of superoxide dismutase (50 U/ml) worsened and catalase (1,800 U/ml) attenuated XO-induced depression of diaphragm contractility. We concluded that XO induced a reduction of low-frequency tension in the fatigued diaphragm, which was mediated directly or indirectly through hydrogen peroxide and was exacerbated to a modest extent with acidosis.
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PMID:Effect of oxidative stress and acidosis on diaphragm contractile function. 927 48

We investigated the effect of hemorrhagic shock and reinfusion on the cardiac function and contractility, plasma CK and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), cardiac chemiluminescence (LV-CL), antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX)] and malondialdehyde (MDA) concentration in anesthetized dogs to determine the role of oxyradicals in cardiac depression and cellular injury in hemorrhagic shock and reinfusion. The dogs were assigned into three groups: I (sham), 4 h duration; II (S + R), 2 h of shock followed by reinfusion for 2 h; III (SOD + S + R), as II but pretreated with PEG-SOD. Hemorrhagic shock was produced by withdrawal of blood to maintain the mean arterial pressure at 50 +/- 5 mm Hg. Cardiac function and contractility were depressed during hemorrhagic shock. Plasma CK, CK-MB and lactate increased during shock. Following reinfusion after 2 h of shock hemodynamic parameters and plasma lactate tended to return towards control values. Plasma CK and CK-MB, PMNL-CL and cardiac MDA, total-, Mn- and CuZn-SOD activity increased while LV-CL decreased. In spite of the increase in the antioxidant reserve, there was oxidative damage. Pretreatment with SOD attenuated the deleterious effects of shock and reinfusion on the cardiovascular function, plasma CK, and CK-MB, PMNL-CL, cardiac MDA, SOD, and LV-CL. Protection was incomplete for cardiovascular function and plasma CK and CK-MB. These results suggest that oxyradicals may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.
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PMID:Cardiac depression and cellular injury in hemorrhagic shock and reinfusion: role of free radicals. 940 75

Pneumotoxic effects of the tri-n-butyl phosphate (TBP) are investigated on rats using biological markers in bronchoalveolar lavage fluid (BALF) and studying key antioxidant enzymes in lung homogenate. Each animal from the experimental group received intratracheally 5 microliters TBP (20% v/v in n-dodecane). Six rats from the control and treated groups are sacrificed on post-treatment days 1, 3, 7, 14, and 28. The lactate dehydrogenase activity, the total protein content and the total cell number in BALF are increased mainly on day 1 after the treatment. The activities of superoxide dismutase and catalase are decreased to day 7 and those of glutathione peroxidase and glutathione reductase on day 1 only. The malondialdehyde content is elevated to day 14. It is concluded that TBP causes moderate toxic injury of the lung parenchyma. The depression of the key antioxidant enzymes and the elevated lipid peroxidation are probably important mechanisms of the lung damage.
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PMID:Antioxidant defense mechanisms in the lung toxicity of tri-n-butyl phosphate. 940 24

In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caused initial augmentation, and subsequent long-lasting depression, of population spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals, because an iron chelator deferoxamine did not block the effect. A catalase inhibitor 3-amino-1,2,4-triazole only modestly attenuated the initial augmentation, suggesting that the effect of H2O2 is not attributable to catalase-dependent O2 generation, either. An N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no influence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depression, indicating that gamma-aminobutyric acid-mediated inhibition is altered during the depression phase. The initial augmentation but not subsequent depression was attenuated by a phospholipase A2/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. These results suggest that H2O2 regulates hippocampal synaptic transmission via multiple mechanisms.
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PMID:Biphasic effect of hydrogen peroxide on field potentials in rat hippocampal slices. 943 Apr 16

Reactive free radical species appear to be involved in the ischemic injury of cardiac muscle, although the mechanisms by which oxygen-derived free radicals affect the heart cell function are not known. In the present study, cultured ventricular myocytes were exposed to an exogenous oxygen radical generating system. The myocyte-enriched, primary cultures were prepared from ventricles of new-born rat heart and exposed to a xanthine/xanthine oxidase (X+XO) system. The transmembrane potentials were recorded with glass microelectrodes. Cell contractions were monitored photometrically. The release of lactate dehydrogenase (LDH) in the medium was analysed. Quantitative measurement and the time course of the radical generation were performed by the electron paramagnetic resonance (EPR) spin trapping technique with the spin trap 5,5-dimethyl-1-pyroline-N-oxide (DMPO). We verified that X and XO alone had no significant functional and biochemical effects. The X+XO system produced a rapid decrease in the action potential amplitude. This effect was accompanied by a strong decrease in contractility and spontaneous rate. The time course of these functional defects were correlated with a progressive efflux of LDH from the cardiomyocytes. Prolonging the exposure to the X+XO system provoked the cessation of the spontaneous beatings and the progressive loss of the resting diastolic potential, together with a near total release of the cellular LDH. The LDH release and the functional depression were both efficiently prevented by catalase. On the contrary, superoxide dismutase (SOD) slowed down but did not protect against the functional and biochemical effects of the free radicals. In comparison, the EPR spectra obtained indicated that the X+XO system was associated with an important generation of superoxide anions but also with a small hydroxyl production. SOD scavenged the superoxide but a small .OH production persisted. Catalase (CAT) did not modify the superoxide generation but decreased the hydroxyl adduct formation. These results suggest that, although the generation of superoxide anions by the X+XO system was higher than the hydroxyl production, the functional injury and enzyme leakage seemed mainly mediated through a hydrogen peroxide-hydroxyl radical pathway. Cultured ventricular myocytes can be thus used as a valuable model to investigate the cellular mechanism of oxidant-induced damage in the heart.
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PMID:Correlation between direct ESR spectroscopic measurements and electromechanical and biochemical assessments of exogenous free radical injury in isolated rat cardiac myocytes. 943 21

1. The b-wave of the electroretinogram (ERG) is a particularly sensitive index of retinal ischemia. The present paper summarizes the changes in the b-wave observed in five in vivo models of retinal ischemia. 2. Although the amount of reduction in b-wave amplitude during ischemia corresponds to the severity of the insult, the degree of recovery of the b-wave during reperfusion depends on the duration of ischemia. 3. A massive release of glutamate, intracellular overload with calcium and enhanced production of free radicals are suggested to be three major pathophysiological processes that contribute to retinal ischemic damage. The b-wave of the ERG represents a functional measure for potential therapeutic efficacy of drugs interacting with these pathophysiological processes. 4. Several glutamate antagonists, such as MK-801, memantine, flupirtine or GYKI 52466, along with the free radical scavengers vitamin E, lipoate, superoxide dismutase and catalase, all reduce the depression of the b-wave during ischemia or accelerate the recovery of the b-wave during reperfusion or both. The calcium channel antagonists nimodipine and levemopamil exert only a slight beneficial effect on the recovery of the amplitude of the b-wave during reperfusion, provided that the blood pressure is not potently reduced.
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PMID:The b-wave of the electroretinogram as an index of retinal ischemia. 951 75

We investigated the lipid peroxidation in depression by determining the markers of this process: melondialdehide, total SH groups and catalase. We used blood samples from inpatients with specific psychiatric symptoms. The medication consist of hypnotic nitrazepam and antidepressant trazodone, using film-coated tablets trazolon, 50 mg once a day, three weeks. In the second part of our experiment, we studied the antioxidant properties of trazodone, using blood samples from healthy subjects. It remain to establish if the free radicals are responsible for the initiation of depression or not.
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PMID:[The lipid peroxidation process in depression: the effect of trazodone]. 952 75


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