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)

Glutathione (GSH) homeostasis and turnover were investigated in totally hepatectomized (HX) rats. A technique is described to remove the liver totally, with preservation of the hepatic portal and vena caval vasculature. Euglycemia could be maintained with hourly infusions of 50 mg 100 g-1 b.m. of glucose after bolus i.v. injection of glucose at the same dose. The efficiency of the animal model was demonstrated by examination of paraclinical blood parameters: progressive increases in total plasma bilirubin and alkaline phosphatase activity were noted after HX; the other parameters tested were predominantly in the normal range during the observation period of 6 hours. Histological examination revealed an acute but reversible impairment of intestine and kidneys. These results indicate that the surgical procedure and postoperative care were able to secure sufficient physiological conditions for the experiments over a longer period. 3 to 6 hours after HX we observed a decreased but stable plasma GSH level in anhepatic rats (about 50% of the control value). The GSH levels of brain and kidney were not changed. With increasing time period after HX the heart and lung GSH levels were depressed. A small depression of muscle GSH concentration was observed 4 and 6 hours after HX. A progressive increase in the concentration of oxidized glutathione was seen in brain and kidney. Our observations could be indicative for a high GSH export capacity of extrahepatic tissues contributing about 50% of the total GSH influx into circulation. Probably, the skeletal musculature is an important GSH origin for plasma.
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PMID:Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues. 144 65

The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The acute pancreatotoxic effects of the plant nitrile 1-cyano-2-hydroxy-3-butene. 188 86

There is controversy as to whether or not the acute cochlear toxicity of ethacrynic acid (EA) is dependent upon its metabolic conversion to EA-cysteine via conjugation with glutathione. In order to investigate this we examined the acute effects of EA on cochlear potentials in guinea pigs in which glutathione levels were decreased by prior administration of (+/-)-buthionine sulphoximine (BSO), an inhibitor of glutamylcysteine synthetase. First, we determined the effects of BSO on hepatic and renal glutathione levels in the guinea pig. Guinea pigs (pigmented animals of both sexes or male albino animals) were killed at intervals up to 72 hr after i.p. administration of 1.6 g kg-1 BSO. Livers, and also kidneys in the case of pigmented guinea pigs, were removed and total glutathione (GSH + GSSG) measured. Glutathione levels reached a nadir in the liver at 24-48 hr (11% of control) and in the kidneys at 24 hr (14% of control) after administration of BSO. Hepatic but not renal levels approached control values by 72 hr. There were no sex or strain differences. Pigmented guinea pigs were anaesthetised and their endocochlear potential and a.c. cochlear potential in response to a 4 kHz tone were measured using an intracochlear microelectrode. The depression of these potentials by i.v. administration of 60 mg kg-1 EA was not affected by administration of 1.6 g kg-1 BSO 24 hr earlier, despite profound depletion of glutathione. Also prior p.o. administration of N-acetyl-L-cysteine did not affect hepatic glutathione levels nor modify the toxicity of EA. These results suggest that the acute cochlear toxicity of EA is not altered by glutathione depletion, a finding which argues against a role for the metabolic activation of EA in its ototoxicity.
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PMID:Glutathione depletion in the guinea pig and its effect on the acute cochlear toxicity of ethacrynic acid. 317 87

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.
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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

1. Oxygen consumption in vitro and persistence in the general circulation of rabbit erythrocytes treated with the cholinesterase inhibitor paraoxon were determined.2. Paraoxon in vitro reduced oxygen consumption below a measureable level within 2 hours. By contrast, the metabolic inhibitor N-ethylmaleimide (NEM) produced complete inhibition within 15 minutes.3. Erythrocytes from rabbits orally dosed with parathion also exhibited marked depression of oxygen consumption.4. Glutathione (GSH) restored oxygen uptake to pretreatment levels within 15 min in erythrocytes previously inhibited with NEM or paraoxon.5. Erythrocytes treated with NEM were rapidly removed from the general circulation while paraoxon treated cells were removed at a rate comparable to untreated cells.
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PMID:Effect of paraoxon on erythrocyte metabolism as measured by oxygen uptake in vitro. 509 Nov 62

Terminal deoxynucleotidyl transferase (TdT) was assayed in 100,000 X g supernatants of homogenized thymus using 3H-dGTP and an oligo p(dA)12-18 primer. 2-Mercaptoethanol (2-ME) caused a depression of activity with rat and mouse thymus extracts but increased activity using bovine or lamb thymus extracts. Glutathione (GSH), L-cysteine and dithiothreitol (DTT) also showed an inhibitory effect with the rat thymus extract. Inhibition was significant at concentrations of sulfhydryl compounds commonly included in TdT assays (1 mM-2 mM).
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PMID:An inhibitory effect of sulfhydryl compounds in the assay of rat and mouse thymic terminal deoxynucleotidyl transferase (TdT). 666 7

Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult (5-month-old) and aged (14-month-old) rats. Depression of levels of glutamine synthetase in the P2 fraction of kidney was observed, which was more severe in aged than young adult rats. Glutamine synthetase is a cytosolic enzyme especially susceptible to oxidative damage. A parallel depression of this enzyme was also seen in the corresponding hepatic fractions. However, levels of glutamine synthetase in the hippocampus were elevated by this exposure. Glutathione levels were depressed in P2 fractions of livers of exposed rats, and also in the corresponding renal fraction. Glutathione concentration was unchanged in cerebral fractions. Overall results were interpreted to imply that pro-oxidant events were elevated in kidney and liver following prolonged inhalation of the solvent mixture. The changes found in brain tissue did not reveal evidence of oxidative stress but, however, suggested that glial activation was taking place.
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PMID:Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit. 749 80

Glutathione (GSH) regeneration was studied in rabbit erythrocytes which were loaded with calcium using ionophore A23187. Calcium-loading induced by A23187 and various concentrations of CaCl2 caused a dose-dependent depression in red cell GSH regeneration. The lowered GSH regeneration was mainly due to reduction of ATP level. In an experiment using haemolysate, the effect of calcium per se was negligible, while magnesium strongly affected GSH regeneration by controlling the rate of hexokinase reaction. These results indicate a possibility that cation perturbation, metabolic decay and oxidative damage are all interrelated in the erythrocyte aging process.
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PMID:Glutathione regeneration in calcium-loaded erythrocytes: a possible relationship among calcium accumulation, ATP decrement and oxidative damage. 755 47

Behavioral depression through inescapable foot shock stress in Swiss albino mice was measured on the basis of their performance in an open field test (OFT) and a forced swimming test (FST). Glutathione (GSH) and various antidepressants (imipramine, maprotiline, fluvoxamine, trazodone, and alprazolam) were able to, either fully or partly, prevent and/or reverse the shock-induced behavioral depression. The GSH level was measured in the cerebral cortex, cerebellum, brain stem, and the hypothalamus in shocked mice to ascertain a possible correlation between brain GSH and stress-induced depression, under conditions of preshock and postshock antidepressant treatments as well as in the absence of the drugs. There was an appreciable depletion of cortical GSH in shocked mice that was corrected to varying degrees by the different antidepressants. The results suggest a close link between stress-induced behavioral depression, increased monoaminergic utilization, oxidative stress, and brain GSH.
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PMID:Glutathione as a cerebral substrate in depressive behavior. 797 87

Toluene and its metabolites have been studied with respect to their reactive oxygen species-enhancing potential in isolated systems and in vivo. The induction of reactive oxygen species (ROS) production was assayed using the probe 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA). Intraperitoneal injection of toluene, benzyl alcohol or benzaldehyde caused a significant elevation in the rate of ROS formation within hepatic mitochondrial fractions (P2). In the brain, only toluene induced ROS formation, while benzyl alcohol and benzaldehyde did not have any effect. Glutathione (GSH) levels were depressed in liver and brain regions from toluene-treated rats. However, no such depression was evident in brains treated with toluene metabolites. P2 fractions from phenobarbital-pretreated rats exhibited a heightened ROS response when challenged with toluene, in vitro. Pretreatment of rats in vivo with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, or sodium cyanamide, an aldehyde dehydrogenase inhibitor, prior to exposure to toluene, caused a significant decrease and increase, respectively, in toluene-stimulated rates of ROS generation in the CNS and liver. Electron spin resonance spectroscopy, employing the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was conducted. Incubation of the spin trap with P2 fractions and toluene or benzaldehyde elicited a spectrum corresponding to the hydroxyl radical. Incubation of benzaldehyde with aldehyde dehydrogenase produced a strong signal that was blocked completely by superoxide dismutase and inhibited partially by catalase, suggesting the presence of superoxide radicals and the involvement of the iron-catalyzed Haber-Weiss reaction leading to the production of hydroxyl radicals. Thus, ROS generation during toluene catabolism may occur at two steps: cytochrome P450 oxidation and aldehyde dehydrogenase oxidation. In addition, GSH may play an important role in protection against the induction of ROS generation in the CNS and liver following exposure to toluene.
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PMID:Free radical induction in the brain and liver by products of toluene catabolism. 839 73


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