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)

We investigated the effects 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 enzymatic activity [superoxide dismutase (SOD), catalase, 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 to four groups: group I (sham), 4 hrs duration; group II, 4 hr of shock; group III, 2 hr of shock, followed by reinfusion for 2 hr; and group IV, as in group III, but pretreated with SOD and catalase. Hemorrhagic shock was produced by withdrawing 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; and cardiac MDA, Mn-SOD, and CuZn-SOD increased, while catalase activity decreased during shock. Following reinfusion after 2 hr of shock, hemodynamic parameters and plasma lactate tended to return toward control values. Plasma CK and CK-MB, PMNL-CL and cardiac MDA, total SOD, Mn- and CuZn-SOD increased further, while LV-CL and GSH-Px decreased. In spite of the increased antioxidant reserve, oxidative damage was noted. Pretreatment with SOD and catalase attenuated the deleterious effects of shock and reinfusion on the cardiovascular function, plasma CK, CK-MB, and lactate, PMNL-CL, cardiac MDA and SOD, and LV-CL. Protection was incomplete for cardiovascular function and plasma CK and CK-MB. These results suggest that oxyradicals (O2-, H2O2) may be partly involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.
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PMID:Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion: effect of SOD and catalase. 783 24

Cardiac myocytes were exposed to concentrations of potassium antimonyl tartrate (PAT) ranging from 1 to 1000 microM for 1 to 24 hr. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release and by monitoring chronotropic depression. Lipid peroxidation was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). PAT produced a concentration- and time-dependent depression in chronotropy and an increase in the release of LDH and TBARS. A 4-hr exposure to 100 microM PAT stopped beating and induced significant increases in TBARS and LDH release in the myocyte cultures. The lipid peroxidation and LDH release induced by 100-200 microM PAT at 4 hr could be prevented by pretreatment of the cardiac myocytes with vitamin E or by the simultaneous addition of other antioxidants. Vitamin E continued to protect against lipid peroxidation up to 18 hr after the addition of 100 microM PAT, but failed to provide significant protection against LDH release at this time-point. Both 50 and 100 microM PAT decreased cardiac myocyte glutathione (GSH) levels after a 4-hr exposure. A series of thiol-containing compounds was evaluated for their effects on PAT toxicity. The addition of dithiothreitol, GSH, and 2-mercaptoethanol afforded some degree of protection against lipid peroxidation and LDH release up to 18 hr after the addition of 100 microM PAT. These results suggest that PAT induces lipid peroxidation in cultured cardiac myocytes but that other mechanisms may contribute to cell death with long-term exposures to PAT. Our results also suggest that PAT interacts with thiol-containing compounds.
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PMID:Antimony-induced oxidative stress and toxicity in cultured cardiac myocytes. 783 69

Several biochemical parameters that reflect the presence of excess levels of reactive oxygen species were modulated in the brains of rats exposed acutely or subchronically to ethanol. These parameters included depression of cytosolic glutathione (GSH) concentration and of glutamine synthetase levels. However, using these indices, there was a significant difference in susceptibility to ethanol in different brain regions. After dietary exposure to ethanol for 12 days, these indices were selectively depressed in the striatum but not in the cerebral cortex or cerebellum. Eighteen hours after a single acute dose of ethanol (4.5 g/kg body wt), the striatum was also the only one of these areas in which proteolytic activity was elevated by ethanol treatment. Two injections of acetaldehyde (300 mg/kg), given 18 and 2 hr prior to tissue preparation, caused a specific reduction of glutamine synthetase in the striatum and a decrease of GSH levels in both striatum and cerebellum. Taken together, the results suggest a distinctive vulnerability of the striatum to ethanol-promoted oxidative events. Rather than ethanol exerting effects directly, the metabolite acetaldehyde may be the primary agent responsible for these changes.
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PMID:Regional selectivity in ethanol-induced pro-oxidant events within the brain. 784 Jul 85

The present studies determined the impact of dietary selenite on glutathione homeostasis in liver and mammary tissue and its relationship to biliary excretion of 7,12-dimethylbenz(a)anthracene (DMBA) conjugates. In Experiment 1, liver and mammary tissue concentration of reduced glutathione (GSH) and activities of gamma-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione S-transferases (GST) were positively correlated with tissue selenium concentration in female rats fed semipurified diets supplemented with sodium selenite (0.05 to 4 mg Se/kg). The magnitude of the response was dependent upon total selenite intake and the tissue examined. Glutathione peroxidase activity did not correlate with tissue GSH concentration. Because both selenite and BHT have been reported to elevate liver GSH, Experiment 2 compared these agents (4 mg Se/kg and 6 g/kg BHT/kg, respectively) on the biliary excretion of DMBA metabolites. Five major biliary DMBA conjugates, three GSH and two beta-glucuronide, were identified. Dietary addition of selenite or BHT enhanced the excretion of these DMBA conjugates by over 100% during the 15-h collection period. These investigations suggest that dietary selenium can alter the concentration of GSH and the activities of three glutathione-dependent enzymes in mammary and liver, accounting for part of the expanded biliary excretion of DMBA conjugates. Enhanced biliary loss of DMBA conjugates likely relates to the reported depression in DMBA binding to mammary cell DNA and the inhibition of DMBA carcinogenesis caused by dietary selenite.
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PMID:Dietary selenite modifies glutathione metabolism and 7,12-dimethylbenz(a)anthracene conjugation in rats. 790 18

Chlorpromazine (CPZ), a phenothiazine, demonstrated both cytoprotective and toxic effects on cardiomyocytes. CPZ markedly reduced cytotoxicity caused by two toxic challenges, each with a distinct cytotoxic mechanism. Lethal cell injury was induced in cultured neonatal cardiomyocytes by either: (1) ionomycin, a Ca2+ ionophore that caused Ca(2+)-dependent cell injury; or (2) ethacrynic acid (EA), a glutathione (GSH) depletor that killed cells primarily via peroxidative damage. Pretreatment with 50 microM CPZ reduced the extent of ionomycin-induced cell death, as measured by lactate dehydrogenase (LDH) leakage, but enhanced the loss of intracellular ATP and collapsed the mitochondrial transmembrane potential (delta psi). In EA-treated cultures, 50 microM CPZ also lowered LDH leakage and diminished the peroxidative damage responsible for the cytotoxicity, but again enhanced the loss of intracellular ATP and collapsed the delta psi. CPZ protection was incomplete and limited to a narrow concentration range that was essentially identical for both toxic challenges. Maximum protection was observed with 50 microM CPZ, yet the amount of residual damage was similar to the degree of injury caused by a mitochondrial uncoupler, carbonylcyanide-m-chlorophenylhydrazone alone. In the absence of either challenge, 50 microM CPZ did not affect cellular energy status or kill the cells, but a higher concentration of CPZ (150 microM) did deenergize unchallenged cardiomyocytes. These data demonstrate that CPZ can reduce cytotoxicity caused by either Ca(2+)-dependent events or oxidative stress. However, even at an optimally protective level, CPZ in combination with either ionomycin or EA deenergized the cells, although neither toxic challenge nor 50 microM CPZ alone seriously affected delta psi. It would appear that intracellular perturbations induced by either challenge promote a depression of mitochondrial function by CPZ, which limits the protective action of the drug. Since both of the challenges used contain toxicologic features exhibited by a wide variety of toxic insults, results of this study have both mechanistic and clinical implications.
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PMID:Chlorpromazine protection against Ca(2+)-dependent and oxidative cell injury. Limitations due to depressed mitochondrial function. 794 52

In the olfactory-bulbectomised rat model of depression, neutrophil phagocytosis was significantly decreased and phagocytosis started later in comparison to sham-operated animals. Both desipramine and lithium chloride treatment significantly reversed the depressed neutrophil phagocytosis and shortened the time to commencement of phagocytosis in drug-treated bulbectomised rats. The catalase and glutathione peroxidase (GSH-PX) activities in bulbectomised rats were decreased, while superoxide dismutase (SOD) was significantly increased. Chronic desipramine and lithium chloride treatment slightly improved catalase activity in the bulbectomised rats. Desipramine significantly reversed the reduction in activity of GSH-PX, but failed to reverse the increased activity of SOD. In contrast, lithium chloride significantly reversed SOD activity to normal values, without affecting GSH-PX activity in the bulbectomised rats.
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PMID:Catalase, superoxide dismutase and glutathione peroxidase activity in neutrophils of sham-operated and olfactory-bulbectomised rats following chronic treatment with desipramine and lithium chloride. 796 55

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

In this study we examined the role of oxygen-derived free radicals in the pathogenesis of acute gastric mucosal lesion induced by obstructive jaundice in rats. Rats were divided into 4 groups as follows: control (sham operation), jaundiced (ligation and dissection of bile duct), vagotomized (truncal vagotomy), and vagotomized with jaundice group. The water immersion restraint procedure was performed. The water immersion restraint procedure was performed. The results obtained are as follows: jaundiced group showed significant increase of ulcer index (UI) and significant decrease of gastric mucosal blood flow (GMBF) and gastric mucosal potential difference (PD). However, intragastric pH (pH) was unchanged compared to the control group. Oxygen radical generating system (gastric mucosal XOD activity and thiobarbiturate acid) and oxygen radical scavenging system (gastric mucosal SOD activity and GSH-px activity) were higher than those of control group. Vagotomized group showed significant increase of pH compared to the control group. Oxygen generating system and scavenging system were unchanged compared to the control group. Vagotomized with jaundice group showed depression of UI and improvement of oxygen radical generating system and scavenging system. However GMBF, PD nad pH were unchanged compared to the jaundiced group. These results suggest that oxygen radical play some role in the development of acute gastric mucosal lesion induced by obstructive jaundice.
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PMID:[Role of oxygen radicals in the pathogenesis of acute gastric mucosal lesion under obstructive jaundice]. 831 98

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 study evaluated potential contributions of daunorubicin and its principle metabolite, daunorubicinol, to the cardiotoxicity of daunorubicin therapy. Daunorubicin (15 mg/kg) or placebo (normal saline) was administered by iv bolus to New Zealand white rabbits and 3 to 4 days later, hearts were removed to measure contractility (dF/dt), concentrations of daunorubicin and daunorubicinol, and evidence of oxidative stress on glutathione and glutathione peroxidase. Contractile function of isolated atria and papillary muscles was depressed (p < 0.05). Daunorubicinol exceeded daunorubicin concentration in the heart (p < 0.005) with a ratio of metabolite to parent drug of 26 in atrial and 32 in ventricular tissue. There was a significant correlation between peak plasma (r = -0.63; p < 0.05) or cardiac concentration (r = -0.78; p < 0.02) of daunorubicinol, but not daunorubicin, and depression of dF/dt in papillary muscles. In separate in vitro studies, daunorubicinol at a concentration (5.5 micrograms/g tissue or 10 microM) approximating that observed ex vivo in heart inhibited Ca2+ uptake into cardiac sarcoplasmic reticulum vesicles by 39 +/- 3%, whereas 10 microM daunorubicin (14-fold higher than actual ex vivo cardiac concentrations) did not demonstrate any detectable inhibition. Daunorubicin treatment failed to significantly alter concentrations of GSH or GSSG or activities of glutathione peroxidase in the heart. Thus, cardiac dysfunction observed 3 to 4 days after a single dose of daunorubicin did not clearly relate to oxidative stress, but was associated with a cardiac concentration of daunorubicinol that appeared sufficiently high to impair Ca2+ metabolism.
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PMID:Daunorubicin-induced cardiac injury in the rabbit: a role for daunorubicinol? 844 96


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