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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37 degrees C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 micrograms X ml-1) was ineffective but catalase (20 micrograms X ml-1) was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 micrograms X ml-1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates. 632 91

Administration of HgCl2 at a dose of 5 mg/kg body weight/day for 15 days to male albino rats brought about a marked depression of the scavenging enzymes viz. glutathione peroxidase and glutathione S-transferase, in kidney. There was an adaptive rise in the levels of catalase and no increased lipid peroxidation was observed. The levels of both glutathione and glutathione reductase were decreased, whereas total thiol increased. In the intoxicated rats, Vitamin-E was effective in bringing back glutathione levels to normal. The adaptation in this group of animals is reflected by increased superoxide dismutase activities. Feeding of Vitamin-E alone could cause a depression of the scavenging enzymes like glutathione peroxidase and glutathione S-transferase along with a slight lowering of glutathione levels.
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PMID:Effects of mercuric chloride on several scavenging enzymes in rat kidney and influence of vitamin E supplementation. 649 53

The mechanism of acute iron cardiotoxicity was investigated in isometrically contracting left atrial strips and right ventricular papillary muscles isolated from rabbit hearts. A 90-min exposure to iron (1.8 mM; as ferrous sulfate) reduced the peak-developed tension and the maximal rate of tension development. The presence of either N-acetylcysteine (20 mM), superoxide dismutase (2000 units/ml), or mannitol (5 mM) prevented this depression of contractility. Catalase (30,000 units/ml) was not protective against the effects of iron. Iron did not decrease myocardial adenosine triphosphate or creatine phosphate contents. The force-frequency relationship (positive staircase phenomenon) was examined in the absence and presence of iron. Iron did not reduce the positive inotropic response evoked by increasing the stimulation frequency, but at higher frequencies iron prolonged the time from peak tension to 90% relaxation. We conclude that acute iron cardiotoxicity may be mediated by free radical generation and does not involve impairment of myocardial high energy phosphate production.
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PMID:Depression of contractility in isolated rabbit myocardium following exposure to iron: role of free radicals. 669 79

A session of hyperbaric oxygenation (HBO) at 2.5 at. abs. conducted for one hour in rabbits with adrenalin heart affection (AHA) immediately after adrenalin administration prevented a decrease in the cardiac contractile function usually developing within two hours after AHA. On the third day of the follow up, rabbits with AHA receiving daily HBO displayed a decrease in the pump and contractile functions as well as in superoxide dismutase (SOD) activity and the antioxidant activity (AOA) of the left ventricle lipids. Combination of HBO sessions with the intra-muscular administration of alpha-tocopherol (50 mg/kg) made the decrease in SOD activity less pronounced and prevented both the fall in lipid AOA and the depression of the heart contractile and pump functions on the third day following AHA. It is suggested that the combined use of HBO and substances increasing the potency of the cell antioxidation system may become one of the principles of reducing HBO side effects and of expanding the potentialities of HBO in treating ischemic and adrenergic heart impairments.
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PMID:[Effect of combined use of hyperbaric oxygenation and alpha-tocopherol on the contractile function and various components of the antioxidant system of the heart after adrenaline lesioning]. 670 Jan 38

An initial event in gram-negative bacteremia is activation of the complement cascade with production of C5a. C5a, in turn, acts as a chemotactic stimulus for leukocytic aggregation and, in conjunction with bacterial products, stimulates the release of oxygen free radicals from leukocytes. We have hypothesized that these oxygen free radicals (.O2-, superoxide anion; .OH, hydroxyl radical; H2O2, hydrogen peroxide) contribute to the characteristic myocardial dysfunction of endotoxin shock, Isolated canine cardiac sarcoplasmic reticulum (SR) was used as a subcellular determinant of mechanical function. SR was incubated for 20 min at 37 degrees C in the presence of phorbol myristate acetate activated leukocytes (A-L) and calcium uptake and Ca2+-adenosine triphosphatase (ATPase) activities were measured. Activated leukocytes significantly depressed SR Ca2+ uptake rates (C = 1.12 +/- 0.05 mumol CA2+/mg-min; A-L = 0.73 +/- 0.05). The addition of catalase (CAT; 10 micrograms/ml) or superoxide dismutase (SOD: 10 micrograms/ml) plus CAT reversed the inhibition of SR Ca2+ uptake. SOD further depressed SR Ca2+ uptake (+SOD = 0.55 +/0 0.04 mumol Ca2+/mg-min). Mannitol had no effect. SR ATPase activity was inhibited with A-L (C = 1.41 +/- 0.04 mumol Pi/mg-min; A-L = 0.84 +/- 0.09). Neither mannitol, nor SOD nor CAT alone had any effect on the depression of SR ATPase activity. SOD plus CAT reversed the ATPase depression induced by A-L. It is concluded that phorbol myristate acetate activated leukocytes via free radical-mediated mechanisms can directly affect function and activity of the excitation-contraction coupling system of cardiac muscle. Free radical scavengers identified hydrogen peroxide as a major mediator of depressed Ca2+ uptake rates. In conjunction with the superoxide anion, hydrogen peroxide contributes to the depressed ATPase activity.
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PMID:Interaction of oxygen free radicals and cardiac sarcoplasmic reticulum: proposed role in the pathogenesis of endotoxin shock. 685 Oct 3

Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates the lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 microgram catalase or 100 microgram SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p less than 0.05), catalase (p less than 0.001) and SOD + catalase (p less than 0.001) on lymphocyte division was significantly greater when given prior to X-irradiation. The lack of an oxygen effect and the inability of SOD and catalase to protect human lymphocytes from X-irradiation suggest that 2- and /or H2O2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis.
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PMID:Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase. 697 18

Paraquat is a widely used herbicide which causes lung injury in animals and humans. To determine whether pulmonary endothelial cell function is altered during the course of paraquat lung toxicity, we measured uptake of serotonin in isolated perfused lungs from rats injected i.p. with 25 mg/kg of paraquat dichloride. In 38 control lungs, serotonin uptake was 0.71 +/- 0.02 (S.E.) and was not significantly different in rats studied 4 and 18 hr after paraquat administration. In contrast, uptakes were 0.60 +/- 0.04 (P less than .05) 24 hr after injection of paraquat. At that time, lung histology and endothelial ultrastructure were unremarkable and dry-to-wet-weight ratios of lungs were normal. Forty-eight hours after paraquat administration, when light and electron microscope evidence of edema and inflammation were extensive, serotonin uptake was further decreased (P less than .01). Two weeks after injection of paraquat, when fibrosis was present, based on lung histology and hydroxyproline content, serotonin uptakes had returned to control levels. Administration of superoxide dismutase prolonged survival but did not protect against paraquat-induced depression of serotonin uptake. These results indicate that paraquat causes an early and reversible depression of pulmonary endothelial cell uptake of serotonin which antedates morphological alterations in lung and the endothelial cell and which is not prevented by treatment with exogenous superoxide dismutase. Uptake of serotonin may provide a sensitive and specific index of injury to the pulmonary endothelium.
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PMID:Depression of serotonin uptake by rat lungs exposed to paraquat. 706 88

Exposure of isolated mouse lung macrophages to 40 and 60 per cent oxygen in tissue culture for 48 hours resulted in significant depression of phagocytosis as compared to air-exposed controls. The impairment of phagocytosis was reversed when the cells were reexposed to normoxic conditions for 48 hours. The impairment of phagocytosis occurred despite significant increases in intracellular superoxide dismutase activity, an enzyme felt to play a protective role in oxygen toxicity. Exposure to 40 and 60 per cent oxygen increased the susceptibility of lung macrophages to functional impairment by 95 per cent oxygen, rather than producing tolerance. The precise biologic and clinical significance of these findings will require additional studies in integrated systems. However, these studies show unequivocal lung macrophage injury with moderate hyperoxic exposure.
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PMID:Impairment of phagocytosis by moderate hyperoxia (40 to 60 per cent oxygen) in lung macrophages. 739 68

Lungs accumulate 5-hydroxytryptamine (serotonin, 5-HT) from the perfusate by a sodium-dependent, energy-requiring, saturable process. The rate-limiting step for uptake is the transport of 5-HT and not its subsequent metabolism to 5-hydroxyindoleacetic acid. Autoradiographic studies indicate that the pulmonary endothelium is the cellular site of uptake. The effect of hyperoxia on lung clearance of 5-HT was studied with isolated perfused and ventilated lungs from rats that were previously exposed to hyperoxia. Lungs were perfused with recirculating electrolyte solution and initial [5-HT] of 0.24 microM. The calculated fractional 5-HT clearance (fracion of 5-HT removed in a single pass) ws 0.77 +/- 0.02 (mean +/- SE: n = 44) for control rats. Mean fractional clearance decreased by 20% in rats exposed to 1 atm O2 for 18 hr and 30% after 4 atmospheres absolute (ata) O2 for 1 hr (p < 0.05). The effects of O2 at 4 ata were in part reversed by exposure to air for 3.5 hr and in part prevented by injection of superoxide dismutase (60 nmole/kg body weight). This degree of O2 exposure at either 1 or 4 ata had no effect on lung content of adenine nucleotides or the distribution of 3H-5HT on autoradiography. Rats maintained for 6 weeks on a vitamin E-deficient diet showed an increased effect of hyperoxia on 5-HT clearance and did not show reversal of changes after 24 hr of air breathing. The results indicate that exposure to elevatd po2 results in reversible depression of pulmonary 5-HT clearance that is potentiated by vitamin E deficiency. This suggests alteration of pulmonary endothelial membrane transport properties due to O2 toxicity.
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PMID:Environmental influences on uptake of serotonin and other amines. 740 97

Production of oxygen-free radicals has been proposed as one pathophysiologic mechanism for postburn cardiac contractile dysfunction in adults. To examine this hypothesis in young subjects, we studied the cardiac effects of polyethylene glycol-superoxide dismutase (PEG-SOD) and PEG-catalase (PEG-CAT), each given as 20 U/g of body weight with fluid resuscitation (Parkland formula), after a third-degree burn constituting 33% of the total body surface area in young (6- to 7-day old) guinea pigs (group 3, n = 12). Fluid-treated burns without scavenger therapy (group 2, n = 15) and sham burn controls (group 1, n = 15) were included. Animals were killed 24 hours postburn, and hearts were studied in vitro (Langendorff). Compared with sham burn controls, fluid-treated burns (group 2) had significant cardiac dysfunction as indicated by a lower peak systolic left ventricular (LV) pressure (LVP: 67 +/- 2 vs. 57 +/- 4 mm Hg, p = 0.01, mean +/- SEM), maximal rate of LV pressure development (+dP/dt max: 1169 +/- 45 vs. 988 +/- 45 mm Hg/second, p = 0.01), and fall (-dP/dt max: 1109 +/- 45 vs. 919 +/- 49 mm Hg/second, p = 0.01). In addition, LV function curves calculated for group 2 were shifted downward and to the right of those calculated for sham burn controls in the direction of contractile depression, p = 0.01. PEG-SOD/PEG-CAT treatment in burns did not significantly improve LVP (60 +/- 5 mm Hg), but scavenger therapy improved +/-dP/dt max values (1112 +/- 74 and 988 +/- 98 mm Hg/second, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of toxic oxygen metabolites in a young model of thermal injury. 747 25


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