UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of chronic cerebral hypoperfusion on the endogenous oxidative stress-related indices, nitrite and nitrate (NOx) concentration, glutathione (GSH) content, superoxide dismutase and catalase activities, and thiobarbituric acid-reactive substances level in the rat striatum, to clarify the participation of oxidative stress in the chronic cerebral hypoperfusion-induced alterations. Our present results indicate that chronic cerebral hypoperfusion produces oxidative stress and disturbs intracellular redox regulation in two distinct phases: at 1 day, "acute" and at 6 weeks, "chronic" alterations after the operation. Therefore, striatal neural cell damage may be mainly attributed to the transient increase of NOx production at 1 day after, and the delayed reduction of muscarinic acetylcholine receptor binding in the striatum may be mostly attributed to the continuous depression of GSH content from the 1st to the 6th postoperative week. In particular, the continuous GSH depression may be considered to accompany the pathophysiology of chronic cerebral hypoperfusion.
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PMID:Chronic cerebral hypoperfusion induces striatal alterations due to the transient increase of NO production and the depression of glutathione content. 1195 36

When male rats were given a single dose of cadmium (Cd) (3.58 mg CdCl2 x H2O/kg, i.p.) 72 hr prior to sacrifice, the testicular 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP), and cumene hydroperoxide (CHPx) decreased significantly as compared to controls. Cd also inhibited reduced glutathione (GSH) level while increasing the lipid peroxidation (LP) level significantly. When the animals were given a single dose of nickel (Ni) (59.5 mg NiCl2 x 6H2O/kg, i.p.) 16 hr prior to sacrifice, significant decreases were observed in EROD and GST activities toward CDNB, EAA, EPNP, and CHPx, and GSH level. No significant alterations were noted in DCNB GST activity and LP level by Ni. For the combined treatment, rats received the single dose of Ni 56 hr after the single dose of Cd and were killed 16 hr later. In these animals, lesser depressions were observed on EROD activity and LP level than those of Cd alone. The combination of metals significantly inhibited GST activities and GSH level but not to a greater degree than noted by Cd or Ni alone. Plasma testosterone levels of Cd-, Ni-, and combination-treated rats decreased significantly compared to controls. The strongest depression was achieved by Cd alone. Cd, both alone and in combination with Ni, increased the tissue Ni uptake significantly. Ni, however, did not produce such an effect on the tissue uptake of Cd in either case. Cd treatment caused interstitial edema and coagulation necrosis in seminiferous tubules and also caused fibrinoidal necrosis in vascular endothelium. Ni treatment did not produce any pathological testicular alterations compared to controls. Combined treatment produced fewer pathological alterations (i.e., only interstitial edema) than that of Cd treatment. These results reveal that the combination of Cd and Ni does nothave a synergistic effect on testicular xenobiotic metabolizing enzymes, and in contrast, Ni has an ameliorating effect on pathological disturbances caused by Cd alone in the rat testis.
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PMID:Combined effects of cadmium and nickel on testicular xenobiotic metabolizing enzymes in rats. 1244 41

The aim of this work was to evaluate the effect of a cycle of estivation and awakening on free radical metabolism in selected organs of the land snail Helix aspersa. Estivation for 20 days induced a 4.9- and 1.8-fold increase in selenium-dependent glutathione peroxidase activity (Se-GPX) and in total glutathione levels (GSH-eq), respectively, in hepatopancreas when compared to activity in active animals 24 h after awakening. Foot muscle Se-GPX activity was also increased 3.9-fold during estivation, whereas GSH-eq did not vary. The activities of other antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione S-transferase) and glucose 6-phosphate dehydrogenase were unchanged in both organs. After 15 min of awakening, the glutathione disulphide (GSSG)/GSH-eq ratio increased significantly by 55% in hepatopancreas, slowly returning to the levels observed during estivation. The higher GSSG/GSH-eq ratio may be caused by increased formation of reactive oxygen species (ROS) during awakening. The levels of thiobarbituric acid reactive substances (TBARS) decreased from 49 to 30.7 nmol g(-1) wet mass in hepatopancreas after 5 min arousal and, after 30 min, TBARS rose significantly to 39.6 nmol g(-1) wet mass, gradually declining thereafter. The levels of lipid hydroperoxides in hepatopancreas and of carbonyl protein in foot muscle both decreased during awakening. The higher levels of products of free radical damage during estivation may have resulted from low levels of ROS formation associated with decreased rates of lipid hydroperoxide detoxification and oxidized protein turnover caused by metabolic depression. The regulation of the antioxidant system during hypometabolism may constitute a mechanism to minimize oxidative stress during cycles of estivation and awakening.
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PMID:Hypometabolism, antioxidant defenses and free radical metabolism in the pulmonate land snail Helix aspersa. 1251 85

Capsaicin is a common dietary constituent and a popular homeopathic treatment for chronic pain. Exposure to capsaicin has been shown to cause various dose-dependent acute physiological responses including the sensation of burning and pain, respiratory depression, and death. In this study, the P450-dependent metabolism of capsaicin by recombinant P450 enzymes and hepatic and lung microsomes from various species, including humans, was determined. A combination of LC/MS, LC/MS/MS, and LC/NMR was used to identify several metabolites of capsaicin that were generated by aromatic (M5 and M7) and alkyl hydroxylation (M2 and M3), O-demethylation (M6), N- (M9) and alkyl dehydrogenation (M1 and M4), and an additional ring oxygenation of M9 (M8). Dehydrogenation of capsaicin was a novel metabolic pathway and produced unique macrocyclic, diene, and imide metabolites. Metabolism of capsaicin by microsomes was inhibited by the nonselective P450 inhibitor 1-aminobenzotriazole (1-ABT). Metabolism was catalyzed by CYP1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Addition of GSH (2 mM) to microsomal incubations stimulated the metabolism of capsaicin and trapped several reactive electrophilic intermediates as their GSH adducts. These results suggested that reactive intermediates, which inactivated certain P450 enzymes, were produced during catalytic turnover. Comparison of the rate and types of metabolites produced from capsaicin and its analogue, nonivamide, demonstrated similar pathways in the P450-dependent metabolism of these two capsaicinoids. However, production of the dehydrogenated (M4), macrocyclic (M1), and omega-1-hydroxylated (M3) metabolites was not observed for nonivamide. These differences may be reflective of the mechanism of formation of these metabolites of capsaicin. The role of metabolism in the cytotoxicity of capsaicin and nonivamide was also assessed in cultured lung and liver cells. Lung cells were markedly more sensitive to cytotoxicity by capsaicin and nonivamide. Cytotoxicity was enhanced 5 and 40% for both compounds by 1-ABT in BEAS-2B and HepG2, respectively. These data suggested that metabolism of capsaicinoids by P450 in cells represented a detoxification mechanism (in contrast to bioactivation).
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PMID:Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells. 1264 34

Depression of metabolism by hypothyroidism decreases oxidant production and thus protects tIssues against oxidant damage. Moreover, it is well-known that abnormal gut motility is a common manifestation in hypo/hyperthyroidism. In this study, we aimed to investigate the putative beneficial effects of methimazole on oxidative injury and dysmotility in a rat colitis model. Methimazole (0.04%) was administered in drinking water starting 15 days prior to induction of colitis. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (30 mg/ml; 0.8 ml) in ethanol. Six days after the induction of colitis, the fecal output was measured and used as an index for colonic motility. All rats were decapitated on the seventh day. The distal colon was weighed and the mucosal lesions were scored. Colonic lipid peroxidation (LP) and glutathione (GSH) measurements were performed. The macroscopic score, the colonic wet weight and LP values of the euthyroid colitis group were found to be higher than those of the control group (P<0.05-0.001). All these parameters were reduced in the methimazole-treated colitis group (P<0.01-0.001). The decrease in colonic GSH levels in the colitis group was completely abolished in the methimazole-treated colitis rats (P<0.01). Induction of colitis increased the average fecal output compared with the control group (P<0.05) and methimazole in the colitis group exaggerated the fecal output (P<0.001). In conclusion, methimazole reduces colonic oxidative injury probably due to hypometabolism, which is associated with a decrease in the production of reactive oxygen intermediates and an increase in the response of antioxidant systems.
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PMID:Methimazole-induced hypothyroidism in rats ameliorates oxidative injury in experimental colitis. 1277 28

Many individuals with cardiovascular diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and alterations in nitric oxide (NO), glutathione (GSH), antioxidant enzyme activities and lipid peroxidation in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) training + nitroglycerin for 8 weeks. BP, heart rate (HR) and respiratory exchange ratio (RER) were monitored weekly for 8 weeks using tail-cuff method and oxygen/carbon dioxide analyzer, respectively. The animals were sacrificed 24 h after last treatments and plasma isolated and analyzed using HPLC, ELISA and UV-VIS spectrophotometric techniques. The results show that exercise conditioning significantly enhanced NO production (p < 0.001), GSH levels (p < 0.001), GSH/GSSG ratio (p < 0.05) and the up-regulation of the activities of catalase (CAT) (p < 0.05), glutathione peroxidase (GSH-Px) (p < 0.001), and glutathione reductase (GR) (p < 0.05), and depression of lactate levels (p < 0.001) in the plasma of the rat. These biochemical changes were accompanied by a significant increase in RER (p < 0.001) without a significant change in BP and HR. Chronic nitroglycerin administration significantly increased NO levels (p < 0.05), GSH levels (p < 0.001), superoxide dismutase (SOD) activity (p < 0.05), GST activity (p < 0.05), and decreased MDA levels (p < 0.05). These biochemical changes were accompanied by a significant decrease in BP (p < 0.05) and without any significant changes in HR and RER. Interaction of exercise training and chronic nitroglycerin treatment resulted in normalization of plasma NO, MDA, lactate levels, and CAT activity. The combination of exercise and nitroglycerin significantly enhanced GSH levels (p < 0.05), and the up-regulation of SOD (p < 0.001), GSH-Px (p < 0.05), GR (p < 0.05) and GST (p < 0.001) activities. These biochemical changes were accompanied by normalization of BP and a significant increased in RER (p < 0.001). The data suggest that the interaction of physical training and chronic nitroglycerin treatment resulted in the maintenance of BP and the up-regulation of plasma antioxidant enzyme activities and GSH levels in the rat.
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PMID:Interaction of physical training and chronic nitroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats. 1284 29

This study was designed to investigate if the impairment of learning and memory induced by acute administration of scopolamine (1.4 mg/kg ip) in rats is associated with altered brain oxidative stress status. The passive avoidance paradigm was used to assess retrieval memory of rats after scopolamine treatment. Following retrieval testing, biochemical assessments of malondialdehyde (MDA), glutathione peroxidase (GSHPx), glutathione (GSH), and superoxide dismutase (SOD) levels/activities as oxidative stress indices were performed. This study also investigated the effect of acute administration of Hypericum perforatum extract (4.0, 8.0, 12.0, and 25.0 mg/kg ip), containing flavonoids with documented antioxidant activity, on brain oxidative status of nai;ve rats treated with amnestic dose of scopolamine. Results showed that administration of 1.4 mg/kg of scopolamine impaired retrieval memory of rats and that such amnesia was associated with elevated MDA and reduced GSH brain levels. In nai;ve rats, which have not been exposed to conditioned fear, scopolamine administration also increased MDA and reduced GSH levels, although with an increase in brain GSHPx activity. Pretreatment of the animals with Hypericum extract (4, 8, and 12 mg/kg) resulted in an antioxidant effect through altering brain MDA, GSHPx, and/or GSH level/activity. Since oxidative stress is implicated in the pathophysiology of dementia, the findings of this study may substantiate the value of scopolamine-induced amnesia in rats as a valid animal model to screen for drugs with potential therapeutic benefit in dementia. Exposure of animals to conditioned fear may be suggested to impair the balance between the rate of lipid peroxidation and the activation of GSHPx as a compensatory antioxidant protective mechanism. It is also concluded that low doses of Hypericum extract, demonstrating antioxidant activity, may be of value for demented patients exhibiting elevated brain oxidative status. Since depression commonly coexists with dementia, Hypericum extract as a drug with documented antidepressant action may also be a better alternative than several other antidepressant medications that have not been evaluated to test their effect on brain oxidative status during amnesia.
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PMID:Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. 1464 52

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or without medication. Therefore, the purpose of this study was to examine the effect of exercise training on BP and HR under the condition of NOS inhibition and to clarify the mechanism of the effect in regard to oxidative stress, antioxidant enzyme activity, and NO production in the plasma of the rat. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitro-L-arginine methyl ester (L-NAME) (10mg/kg, s.c. for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) and heart rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24h after last treatments, plasma isolated and analyzed. The results show that exercise conditioning resulted in enhanced NO production (120% of control), GSH levels (110% of control), GSH/GSSG ratio (124% of control) and the up-regulation of catalase (CAT) (225% of control), glutathione peroxidase (GSH-Px) (161% of control), glutathione reductase (GR) (142% of control) and glutathione-S-transferase (GST) (189% of control) and depression of malondialdehyde (MDA) (90% of control) and lactate (75% of control) in plasma of the rat. These biochemical changes were accompanied by no significant change in BP but slight increase in HR. Chronic L-NAME administration resulted in depression of NO (84% of control), GSH (90% of control), GSH/GSSG ratio (76% of control), the down-regulation of superoxide dismutase (SOD) (67% of control), GST (74% of control), and GR (90% of control). Plasma CAT and GSH-Px activities, MDA and lactate levels were significantly increased in L-NAME treated rats. The biochemical changes were accompanied by increase in blood pressure and heart rate. Interaction of exercise training and chronic NOS inhibitor treatment resulted in normalization of plasma NO levels, GSH/GSSG ratio, SOD and GST activities, and the up-regulation of, CAT, GSH-Px, and GR activities. The interaction resulted in depletion of plasma MDA levels compared to L-NAME treated group. The biochemical changes were accompanied by decrease in BP and HR compared to L-NAME treated group. The data suggest that the exercise training attenuated the oxidative injury caused by NOS inhibitor by increasing the plasma NO levels, GSH/GSSG ratio and up-regulating the antioxidant enzyme and lowering the BP and HR in the rat.
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PMID:Interaction of exercise training and chronic NOS inhibition on blood pressure, heart rate, NO and antioxidants in plasma of rats. 1464 3

Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of l-arginine to ameliorate the oxidative stress and metabolic changes after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with 100 mg kg(-1) of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus. Hyperglycaemia and hypercholesterolaemia were observed in serum after 7 days of alloxan treatment. This was associated with a depression of glutathione (GSH) concentration as well as superoxide dismutase (SOD) and catalase (CAT) activities in the liver and brain. In addition, the thiobarbituric acid-reactive substances (TBARS) were significantly elevated, indicating increased lipid peroxidation and oxidative stress in the same tissues. Administration of 100 mg kg(-1) l-arginine for 7 days either before or after alloxan injection significantly ameliorated the oxidative stress evidenced by a lower TBARS and a higher level of the endogenous GSH concentration and SOD and CAT activities than alloxan-treated rats. These effects were paralleled by marked protection and partial prophylaxis against alloxan-induced hyperglycaemia and cholesterolaemia. Thus, these results showed that exogenously administered l-arginine might improve the clinical manifestation of diabetes mellitus and decrease the oxidative stress in the liver and brain. In addition, the study supports the beneficial effect of l-arginine, which might be attributed to its direct, NO-dependent antioxidant capacity and/or NO-independent pathways.
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PMID:L-Arginine ameliorates oxidative stress in alloxan-induced experimental diabetes mellitus. 1505 3

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.
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PMID:Antioxidant enzyme activities and oxidative stress in affective disorders. 1507 17

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