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)

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

This investigation aimed to determine whether contractile dysfunction of the myocardium could be produced upon generation of free radicals in the anaesthetised rat. The enzyme xanthine oxidase, combined with its substrate purine and an iron source, was used to generate free radicals in the venous circulation. The suspended form of xanthine oxidase, with substrate, produced a transient, significant depression in the contractile indices dP dt-1 max and dP dt-1 P-1 and arterial blood pressure, 1146 +/- 87 mm Hg s-1, 9 +/- 1 s-1, and 18 +/- 1 mm Hg, respectively. This could not be attenuated by the enzymatic free radical scavengers superoxide dismutase and catalase. Furthermore, the suspended xanthine oxidase alone or its vehicle were able to produce a similar effect to that of the complete free-radical-generating system. The maximum soluble dose of the crystalline form of the enzyme when employed in the generating system had no effect upon administration despite its production of superoxide radicals in vitro. These results suggest that the haemodynamic effects of the free-radical-generating system containing the suspended form of xanthine oxidase were due to the effects of its vehicle and that the free-radical-generating system containing the crystalline form of the enzyme did not produce sufficient free radicals in vivo to modify myocardial contractility.
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PMID:Effects of the xanthine oxidase system on cardiac function in anaesthetised rats. 840 24

Platelet thromboxane (TX) production was examined in response to dietary copper. Groups of eight rats were fed copper-deficient, -marginal, and -adequate diets providing 0.5, 1.7, and 7.5 micrograms Cu/g, respectively, with controlled dietary Se and vitamin E. Platelets were purified and washed by centrifugation. Separate platelet samples from each rat were challenged with 10 micrograms/ml of collagen and 1 unit/ml (27.3 nM) of thrombin in Tyrode's buffer, 2.0 mM Ca2+. Platelet copper-dependent superoxide dismutase (CuSOD) activity showed a significant depression with reduced diet copper, but platelet glutathione peroxidase activity was unaffected. Challenged platelet TX production showed a significant 1.5- to 2.5-fold increase in response to both dietary copper deficiency and marginality, with highly significant negative correlations between challenged platelet TX production and platelet CuSOD activity and between TX production and copper status (liver copper). Endogenous (unchallenged) platelet lipid hydroperoxide concentrations, measured as free fatty acid hydroperoxides by a glutathione-disulfide-specific glutathione reductase recycling assay, showed a nonsignificant 47-67% increase in copper deficiency. Pooled data showed a significant 71% increase in platelet lipid hydroperoxides in copper deficiency. Platelet TX production showed a significant correlation with endogenous lipid hydroperoxides. The results suggest that dietary copper insufficiency increases platelet TX synthesis through changes in CuSOD in a dose-responsive (diet copper and platelet CuSOD activity) manner, and that platelet TX synthesis is influenced by lipid hydroperoxides (peroxide tone).
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PMID:Thromboxane production in copper-deficient and marginal platelets: influence of superoxide dismutase and lipid hydroperoxides. 842 6

Experiment was carried out on a total of 160 male Wistar rats. Paraquat was instilled per os intragastrically by a metal probe, in aqueous solution, at a daily dose of 0.46 mg/kg body wt given five times a week for 4 months. Directly upon termination of paraquat intake the animals received a single external whole-body exposure to 4 Gy of ionizing radiation. Changes in the parameters studied were recorded on Post-treatment Days 1, 5, 10, and 30. In bronchoalveolar lavage fluid (BALF), paraquat treatment alone was found to elevate lactate dehydrogenase (LDH) activity and content of thiobarbituric acid (TBA) reactants; lung homogenate from this treatment group showed diminution in superoxide dismutase (SOD) and catalase (CAT) activities and in content of nonprotein sulfhydryl groups (NPSH) on Days 1 and 5. Irradiation alone produced less substantial changes. With combined exposure to paraquat and radiation, there was more marked and more prolonged depression of the three parameters (SOD, CAT, and NPSH) of lung antioxidant defense and synergic increase in BALF content of TBA reactants and LDH activity.
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PMID:Synergic lung changes in rats receiving combined exposure to paraquat and ionizing radiation. 843 66

This study examined the role of oxygen radicals in pial arteriolar changes during cortical spreading depression (CSD). CSD was induced by microinjection of 5% KCl in anesthetized adult rabbits. Pial diameter was measured with a closed cranial window and intravital microscopy. During control CSD (n = 12), the dilation amplitude and area were 55 +/- 14% and 693 +/- 69 mm2 (baseline = 76 +/- 14 microns), respectively. Oxygen radical scavengers, superoxide dismutase (SOD; 105 U/ml, topical application; n = 5) or oxypurinol (50 mg/kg i.v.; n = 7), did not alter the dilation amplitude and area or change onset latency during CSD. Further, SOD and oxypurinol did not prevent NG-nitro-L-arginine from attenuating arteriolar dilation during CSD (n = 12). We conclude that oxygen radicals do not play a role in the transient dilation of cerebral arterioles during CSD.
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PMID:Oxygen radicals do not play a role in arteriolar dilation during cortical spreading depression. 853 May 51

108 guinea pigs were infected with M-tuberculosis 2 weeks later 36 of them were put on treatment with rifampicin and isoniazid, the rest served as untreated control. The comparison was made of mixed population of all the cells isolated from bronchoalveolar lavage versus pure fraction of alveolar macrophages (AM) by spontaneous and BCG killed culture-stimulated NBT-test, activity of superoxide dismutase and catalase, levels of malonic dialdehyde. Estimations were conducted 1 day, 1, 2 and 6 weeks after inoculation in untreated animals and after 1 months of treatment in treated animals. AM lost ability for stimulation to the end of 24 h period since inoculation. 1-2 weeks later metabolic depression and complete areactivity occurred. Mixed population within postinoculation week 1 mobilized its defense potential. In extensive generalized tuberculosis all the cells of the respiratory tract worked for self-defense and lost protecting abilities. Specific chemotherapy reestablished functional status of both AM and cell population on the whole.
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PMID:[Oxidative metabolism changes in respiratory tract cells of guinea pigs during natural development of experimental tuberculosis and under specific chemotherapy]. 865 93

A crude extract containing some toxic furanoterpenoids was isolated from F. solani infected sweet potatoes. Chronic administration of the crude extract to male albino rats at a dosage of 1 mg/kg body weight/day for 21 days brought about a sharp increase in the thiobarbituric acid reactive substances and a depression of glutathione levels in the lung and liver homogenates. The antioxidant defense system was affected as evident from a significant fall in the activities of the enzymes, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase. Such an alteration could be the reason for the lung and liver damage caused by these toxic furanoterpenoids.
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PMID:Oxidative stress in rat liver and lung induced by furanoterpenoids isolated from Fusarium solani infected sweet potatoes. 869 9

A new method was developed that reduces the intracellular iron content of cells grown in serum-containing culture without involving the significant uptake of iron-chelating agents into cells. Negatively charged bathophenanthrolinedisulfonate (BPS), together with ascorbate, caused cells to lose much of their cellular iron without causing much depression in HL-60 or H9c2 (2-1) cell proliferation over a 48-h period. When added to serum supplemented RPMI-1640 culture media, BPS and ascorbate efficiently reduced and competed for iron in Fe(III) transferrin to form Fe(II)(BPS)3. The reaction also occurred with purified human iron-transferrin. When cells were incubated with growth medium containing serum that had been treated with BPS and ascorbate for 24 h, little or no BPS2- or Fe(II)(BPS)(4-)3 entered the cells, according to direct measurements and in agreement with the highly unfavorable 1-octanol/water partition coefficients for these molecules. However, iron was mobilized out of both cell types. After 24 h incubation of cells in this medium, there was no change in the activities of catalase and superoxide dismutase, or in the concentration of glutathione. Glutathione peroxidase was elevated 9%. Using HL-60 and H9c2 (2-1) cells made iron deficient with BPS and ascorbate, HL-60 cells grown in defined-growth media in the absence of iron-pyridoxal isonicotinoyl hydrazone, or Euglena gracilis cells maintained in a defined medium that was rigorously depleted of iron, it was shown that the cytotoxicity of adriamycin is markedly dependent on the presence of iron in each type of cell. Similar results were obtained when HL-60 cells were grown in RPMI-1640 culture medium and serum that had been incubated for 24 h in BPS and ascorbate and then chromatographed over a Bio-Rad desalting column to remove small molecules including BPS, ascorbate, and Fe(II)(BPS)3.
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PMID:Depletion of cellular iron by bps and ascorbate: effect on toxicity of adriamycin. 872 Sep 2

The aim of this study was to determine the role of oxidative stress on c-fos and hsp70 gene expression in transgenic (Tg) mice overexpressing CuZn-superoxide dismutase (SOD-1) following traumatic brain injury (TBI). hsp70 mRNA, as investigated using in situ hybridization, was induced around the lesion at 4 and 24 h, but not at 1 and 48 h, in both Tg and non-transgenic (nTg) mice littermates. The degree of hsp70 induction was somewhat greater in nTg than Tg mice at 4 and 24 h after TBI. c-fos mRNA was induced throughout cortex, hippocampus, caudate putamen and the ventricular wall in Tg and nTg mice. TBI induced c-fos bilaterally in the cortex in both animals. There was a time-dependent difference in cortical c-fos expression between nTg and Tg mice. The induction of c-fos mRNA in the striatum was greater in nTg at 24 h and decreased in both animals by 48 h. Edema of the injured cortex was significantly attenuated in Tg mice at all time points (1-48 h). These data show that the degree of hsp70 induction and the degree, extent, and duration of c-fos induction produced by TBI are affected by levels of superoxide dismutase activity. It is proposed that superoxide radicals affect spreading depression and brain edema produced by TBI and that this effect may either directly or indirectly modulate the expression of the c-fos and hsp70 genes after TBI.
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PMID:Expression of c-fos and hsp70 mRNA after traumatic brain injury in transgenic mice overexpressing CuZn-superoxide dismutase. 875 Aug 88

Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced release was completely blocked. We conclude that elevated levels of H2O2 with exercise are capable of damaging one or more proteins of the excitation-contraction coupling process to produce a disruption in function that can account, at least in part, for the long-lasting effects of fatiguing stimulation.
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PMID:Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers. 920 78


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