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)

The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to 10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl, thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion, chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2-deoxyguanosine were significantly increased relative to controls, whereas at higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The administration of the pesticide mixture dose dependently reduced benzo(a)pyrene hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and thiol transferase activities in the liver. The results show that the pesticide mixture induced free radical DNA damage at low doses. However, at higher doses it produced a depression of cellular metabolism, inhibiting a further expression of oxidative damage.
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PMID:Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enzymes in rat liver. 772 83

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

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

In 20 patients receiving cold crystalloid cardioplegia (n = 10) or cold blood cardioplegia (n = 10) during elective coronary artery bypass grafting, the atrial myocardium was tested for glutathione-related antioxidant defenses and lipid peroxidation. In both groups, ischemia and reperfusion induced a significant increase in lipid peroxidation values (p < 0.05) that was associated with a depression of nonprotein thiol compound levels (p < 0.05). Compared with the cold crystalloid cardioplegia-treated patients, the cold blood cardioplegia-treated patients showed a lower lipid peroxidation (p < 0.05) and higher values of nonprotein thiol compounds (p < 0.05). Moreover, a significant ischemia and reperfusion-dependent activation of glutathione transferase was observed only in the cold crystalloid cardioplegia-treated patients. Selenium-dependent glutathione peroxidase and glutathione reductase activities did not change after release of the aortic cross-clamp and did not differ between the two groups. The highest postoperative plasma level of the myocardial-specific isoenzyme of creatine kinase was significantly more elevated in the cold crystalloid cardioplegia patients. Overall, these tissue biochemical features indicate a lower oxidant burden in the myocardium of cold blood cardioplegia-treated patients, a finding suggesting superior protection for the ischemic and reperfused human myocardium also through antioxidant-type mechanisms, apparently medicated by the antioxidant capacity of erythrocytes and specific plasma molecules.
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PMID:Blood cardioplegia reduces oxidant burden in the ischemic and reperfused human myocardium. 801 Jul 96

Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 +/- 2.1 microns (MMAD +/- delta g). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of > or = 300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM > or = 40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures > or = 10 mg/m3. Lung instillations at 250, 500, and 1000 micrograms of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6x control). However, rats gavaged with VDM had serum enzyme levels 10-100x control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.
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PMID:Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage. 812 3

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetyl-L-cysteine in endotoxemia. 820 75

To understand the mechanism for the expulsion of Nippostrongylus brasiliensis from rats, age-dependent variations in the metabolism of reactive oxygen species in the parasite and the host intestines were examined. N. brasiliensis showed an age-dependent increase in its susceptibility to xanthine-xanthine oxidase and t-butyl hydroperoxide generated oxidants as well as to H2O2. Protection obtained with several scavengers suggested that the worms were damaged by the combined action of oxidants generated by the in vitro systems employed. The level of superoxide dismutase in the nematode and its release into the surroundings exhibited a marked depression with advancement of age. No such alteration was, however, recorded for catalase and glutathione peroxidase. An appreciable decrease in the level of reduced glutathione in older N. brasiliensis appears to render them prone to oxidant attack. The rat intestines, on the other hand, exhibited an appreciable depression in catalase and a reduced glutathione content with progress of the infection. Vitamin E levels were elevated. The release of O2-. and H2O2 by the intestines was also found to be greater during later stages of the infection. The combined effect of the changes observed in N. brasiliensis and in the rat intestines may be at least partly responsible for expulsion of the nematode from the rats after day 10.
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PMID:Role of reactive oxygen species in expulsion of Nippostrongylus brasiliensis from rats. 838 14

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

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

In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.
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PMID:Myocardial antioxidant defenses during cardiopulmonary bypass. 846


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