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

Experimental studies have demonstrated that myocardium reperfused after reversible ischemia exhibits prolonged depression of contractile function ("stunning"), which is associated with various ultrastructural, biochemical, vascular and other functional abnormalities. Clinical observations suggest that stunning occurs in many situations (for example, rest and exercise-induced angina, myocardial infarction with early reperfusion, open heart surgery, transplantation) and thus may contribute significantly to morbidity among patients with coronary artery disease. In recent years an increasing number of studies have provided indirect evidence that postischemic myocardial dysfunction may be mediated in part by the generation of reactive oxygen species, such as superoxide radical (.O2-), hydrogen peroxide (H2O2) and hydroxyl radical (.OH). Thus, it has been shown that the recovery of the stunned myocardium is enhanced by agents that either scavenge oxygen metabolites, such as superoxide dismutase and catalase, N-2-mercaptopropionylglycine and dimethylthiourea, or prevent their generation, such as allopurinol, oxypurinol and desferrioxamine. More recent experiments utilizing electron paramagnetic resonance spectroscopy have directly demonstrated that reperfusion after a reversible ischemic episode is associated with a burst of free radical production. At present, the evidence supporting the free radical hypothesis is suggestive but not conclusive. Definitive demonstration of the role of oxy-radicals will require careful studies measuring the production of these species in conscious animal models of postischemic dysfunction. If confirmed, the free radical hypothesis will provide not only new important insights into the pathophysiology of ischemic injury, but also a rationale for developing clinically applicable interventions.
 ...
PMID:Oxygen-derived free radicals and postischemic myocardial dysfunction ("stunned myocardium"). 328 76

Lipid peroxidation and the activity of the antioxidant system were studied in the mucous membrane of the stomach of 60 patients with peptic ulcer. Maximum activation of lipid peroxidation was at the ulcer edges and in the surrounding mucosa. In the same regions the following changes were noted: an increase in the activity of superoxide dismutase, depression of activity of glutathione peroxidase and glutathione reductase, a decrease in the amount of reduced glutathione and accumulation of oxidated glutathione. Activation of lipid peroxidation and disruption of activity of the antioxidant system in the mucous membrane of the stomach were considered to be important pathogenetic factors leading to a chronic and recurrent course of peptic ulcer.
 ...
PMID:[Lipid peroxidation and the antioxidant enzyme system of the gastric mucosa in peptic ulcer]. 336 59

Rats with streptozotocin-induced diabetes mellitus (DM) are resistant to aminoglycoside (AG) nephrotoxicity presumably because of defective transport and accumulation of drug by proximal tubular cells. To test this hypothesis we injected DM rats with saline or with gentamicin, 100, 200, and 400 mg/kg per day for 6 days, to determine if the renal cortical concentration of gentamicin could be raised to toxic levels. Nephrotoxicity was assessed by monitoring for evidence of accelerated lipid peroxidation in the renal cortex, for elevation of the serum creatinine concentration, and for evidence of proximal tubular cell injury and necrosis by light and electron microscopy. At 100 mg/kg per day renal cortical gentamicin was 454 +/- 85 micrograms/g. Except for an increase in renal cortical phospholipids these rats manifested no evidence of accelerated lipid peroxidation or elevation of serum creatinine. At 200 mg/kg per day renal cortical gentamicin rose to 636 +/- 20 micrograms/g. These rats manifested mild functional and morphological evidence of toxicity. At 400 mg/kg renal cortical gentamicin rose to 741 +/- 43 micrograms/g. These rats developed severe nephrotoxic injury as manifested by a marked increase of lipid peroxidation evident by an increase of malondialdehyde from a control level of 0.48 +/- 0.02 to 1.72 +/- 0.12 nmole/mg protein, a shift from unsaturated to saturated fatty acids esterified in renal cortical phospholipids, depression of superoxide dismutase and catalase, and a shift from reduced to oxidized glutathione. The serum creatinine rose from a baseline level of 0.24 +/- 0.01 to 0.46 +/- 0.05 mg/dl. Light and electron microscopy revealed enlarged lysosomes distended with typical myeloid bodies and extensive proximal tubular cell necrosis. These observations provide compelling evidence in support of the view that the resistance of DM rats to AG nephrotoxicity is causally linked to the low rate of drug uptake by renal proximal tubular cells. When the renal cortical concentration reaches a critical level, it elicits a pattern of toxic injury indistinguishable from that of nondiabetic rats. Thus, there is nothing inherent to the diabetic state that prevents AGs from causing their usual adverse effects on the metabolism of renal proximal tubular cells once they gain access in sufficient quantity into these cells.
 ...
PMID:Induction of nephrotoxicity by high doses of gentamicin in diabetic rats. 342 18

To delineate the active free radical species mediating the toxic effects of autoxidizing dihydroxyfumarate (DHF), isolated rabbit right ventricular papillary muscles were exposed to 4.5 mM DHF in the presence of FeCl3, ADP and bovine albumin. In the absence of free radical scavengers a 47.3 +/- 11.5% (mean +/- standard deviation) depression in contractile force was noted over 60 minutes. Neither the combination of superoxide dismutase (SOD) 3,200 u/cc and catalase (CAT) 2,950 u/cc nor mannitol 0.1 M provided statistically significant protection. Deferoxamine mesylate (DFX) 10 mg/cc (15 mM) did provide significant protection of muscle function both in the presence and absence of SOD and CAT (p less than 0.01). The degree of protection conferred by DFX alone was statistically similar to that of DFX with SOD and CAT. This data suggests the involvement of an iron-oxygen complex not dependent on superoxide or hydrogen peroxide for its formation and not readily scavenged by mannitol. The perferryl ion may be representative of such a species. Alternatively, a reactive complex similar to the 'Crypto-OH' radical proposed by Youngman may be formed by the reaction of DHF with iron and oxygen.
 ...
PMID:The effects of dihydroxyfumarate on isolated rabbit papillary muscle function: evidence for an iron dependent non-hydroxyl radical mechanism. 344 Dec 52

The preventive effects of intravenously administered superoxide dismutase (SOD) and of SOD combined with sucrose on acute renal failure were investigated in rat kidneys exposed to 45 min of warm ischaemia. Superoxide dismutase (20 mg) given just before primary ischaemia and in the early recirculation phase was found to ameliorate the red cell aggregation in the renal medulla, in particular, in the inner stripe of the outer zone the volume of trapped red cells decreased from 11.2 +/- 1.6% in untreated animals to 0.02 +/- 0.001%, thus allowing improved restoration of medullary blood flow. This was also accompanied by an expected restoration of the urine osmolality reaching almost 400 mOsm kg-1 after administration of SOD + sucrose. Superoxide dismutase also restored the capillary macromolecular permeability as evidenced by normalization of plasma to lymph transport of proteins. Micropuncture studies showed that in ischaemically damaged but untreated kidneys the tubules were obstructed and that the proximal tubular pressure rose to such a level that the net driving force for filtration approached zero. This explains the marked decrease in glomerular filtration rate (GFR) from a normal value of about 1 ml min-1 to 0.01 +/- 0.02 ml min-1. After treatment with SOD the tubules were still largely obstructed, resulting in a depression of the net driving force and a decrease in single nephron glomerular filtration rate (SNGFR) to about 11 nl min-1, that is, to only 25% of the normal SNGFR. The total filtration was 0.09 +/- 0.04 ml min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prevention of ischaemic acute renal failure with superoxide dismutase and sucrose. 363 Jul 18

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

The oxygen consumption of cerebral arterioles from anesthetized cats was measured using the Cartesian diver microrespirometer following in vitro incubation with 200 micrograms/ml of arachidonate or 50 micrograms/ml of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE). Both agents depressed oxygen consumption severely. This effect was inhibited completely by a combination of superoxide dismutase (SOD) and catalase, indicating that it is mediated by oxygen radicals. Similar depression of oxygen consumption was observed during incubation of the vessels with xanthine oxidase and acetaldehyde as substrate. This enzymic system is known to generate superoxide and hydrogen peroxide. The effect of xanthine oxidase was also partially inhibited by SOD and catalase. The effect of arachidonate was partially inhibited by cyclooxygenase inhibitors. The effect of lipoxygenase inhibitors could not be adequately tested because they depressed oxygen consumption by themselves. Prostaglandins H2 and E2 had no effect on arteriolar oxygen consumption. The results show that arachidonate and 15-HPETE in high concentration depress cerebral arteriolar oxygen consumption via an oxygen radical-mediated mechanism. Furthermore, the radical is generated in the vessel wall and does not require either the brain parenchyma or the formed elements of the blood or the meninges for its production.
 ...
PMID:Reduction in cerebral arteriolar oxygen consumption by arachidonate. 392 Sep 21

To further delineate the mechanisms underlying murine pulmonary defenses against bacterial infection, we studied the effects of antioxidant enzymes and hydroxyl radical scavengers on pulmonary clearance processes. Intratracheal injection of catalase and superoxide dismutase resulted in prolonged intraalveolar residence of the enzymes, but caused no decrease in rates of clearance of either Staphylococcus aureus 502A or Pseudomonas aeruginosa PAO1. In contrast, dimethylsulfoxide and dimethylthiourea caused significant depression of clearance of P. aeruginosa without altering clearance of S. aureus. These results provide further differentiation between clearance processes affecting gram-negative and gram-positive bacteria and suggest that murine clearance of gram-negative organisms may be in part mediated by reactions which generate hydroxyl anion. In vivo administration of agents which inhibit hydrogen peroxide-, superoxide-, or hydroxyl anion-mediated reactions do not alter normal clearance of S. aureus.
 ...
PMID:Modulation of pulmonary clearance of bacteria by antioxidants. 398 94

Adjuvant arthritis was induced in rats by the injection of Mycobacterium tuberculosis, and its severity was scored according to the macroscopic findings of the legs, tail, and ears. The average score so obtained was lower in SOD-injected rats than in the control group. The depression of albumin/globulin ratio was inhibited significantly in rats treated with 10.0 mg/kg of SOD. The levels of acid phosphatase and beta-glucuronidase were elevated after the administration of an adjuvant, and these lysosomal enzymes showed a remarkable increase in the control rats, while the elevation was inhibited in rats injected with 10.0 mg/kg of SOD. The levels of TBA-reactive substances in the sera and synovia were elevated at 2 weeks after the injection of adjuvant and decreased thereafter. In rats injected with 5.0 mg/kg or 10.0 mg/kg of SOD, the increase in both serum and synovial levels of TBA reactants was inhibited significantly. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation due to superoxide, and that SOD may be beneficial for the treatment of arthritis.
 ...
PMID:The increase of lipid peroxidation in rat adjuvant arthritis and its inhibition by superoxide dismutase. 401 32

Effects of exogenous antioxidant administration (0.5% and 2% ascorbate, beta-carotene and alpha-tocopherol in sucrose) on life-span, metabolic rate, activities of superoxide dismutase and catalase, levels of glutathione, inorganic peroxides and chloroform-soluble fluorescent material (lipofuscin) were examined in adult male houseflies. Administration of antioxidants at a level of 0.5% did not affect life-span, whereas, 2% ascorbate and alpha-tocopherol decreased average life-span. Metabolic rate of flies was unaffected, except by 2% ascorbate, which caused a decrease. Superoxide dismutase activity was depressed by 2% ascorbate at all ages, and by beta-carotene and alpha-tocopherol in older flies. Catalase activity was unaffected except by alpha-tocopherol at younger ages. Glutathione concentration was decreased by ascorbate and beta-carotene at both concentrations administered. Inorganic peroxides (H2O2) were increased by 2% beta-carotene and alpha-tocopherol. Only high concentrations of ascorbate and beta-carotene decreased the level of soluble fluorescent material. Results suggest that administration of exogenous antioxidants causes a compensatory depression of endogenous defenses.
 ...
PMID:Effects of exogenous antioxidants on the levels of endogenous antioxidants, lipid-soluble fluorescent material and life span in the housefly, Musca domestica. 406 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>