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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of immature rats to lead acetate results in hemorrhagic encephalopathy of variable evolution. As the maintenance of adequate protection against peroxides may be critical in this condition, the activities of selenium-glutathione peroxidase and catalase in cerebrum and cerebellum of suckling rats poisoned with lead acetate were studied from day six to day sixteen post-exposure. Age-related decreases of glutathione peroxidase and catalase activities in both controls and lead poisoned animals were observed. An increase in catalase activity was observed in cerebrum and cerebellum of lead-treated rats compared to controls. Glutathione peroxidase activity did not change significantly in cerebrum over the period studied. By contrast, glutathione peroxidase activity in cerebellum of lead-treated rats remained at about twice the control level over most of the study period. This apparent increase in glutathione peroxidase activity may be due either to a slower ontogenic decrease of its specific activity or to enzyme induction in response to oxidant stress in cerebellum.
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PMID:Effects of lead acetate on cerebral glutathione peroxidase and catalase in the suckling rat. 277 Nov 98

An influence of intermittent hypoxia (IH) on antioxidant enzymes activity was investigated in 42 patients, aged 48.2 +/- 1.8 years, with 1-2-nd stage of dyscirculatory encephalopathy (DE) in the presence of I-II stage of arterial hypertension (AH). Patients with arterial pressure below 145/85 mmHg receiving basic antihypertensive drugs treatment were included in the study. Before IH, the patients showed increased total oxidant activity (TOA) as well as concentration of thiobarbituric acid reactive substances (TBRS) in blood plasma and reduced activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP) in erythrocytes comparing to control group (14 healthy subjects). In 27 patients, it was combined with increased peak systolic and peak diastolic blood flow rate in middle cerebral artery according to Doppler examination. After 10 days hypoxia training (60 min daily atmospheric air breathing alternated with 9-10 V% O2 hypoxic mixture breathing), TOA and TBRS were decreased by 39% and 25% respectively, whereas enzymes activity was increased as follows: SOD--by 29%; CAT--by 18%; GP--by 38%. The treatment resulted in reduction of peak systolic and peak diastolic blood flow rate in the meddle cerebral artery, decrease of frequency of headache episodes and in improvement of nighttime sleep and short-term memory. The results demonstrate a possibility for correction of oxidative homeostasis disturbances in patients with DE on the background of AH and can be beneficial for DE prevention and treatment.
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PMID:[Intermittent hypoxia in the treatment of dyscirculatory encephalopathy]. 1249 93

Chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, may be responsible for serious adverse effects like encephalopathy in ifosfamide chemotherapy. In this study, we demonstrate that chloroacetaldehyde, but not ifosfamide, induces cell death in human osteosarcoma Saos-2 cells and we investigated the mechanism by which this occurs. Chloroacetaldehyde above 30 micromol/l induced significant cell death in a time-dependent manner. Thiol compounds such as N-acetyl cysteine, glutathione and dithiothreitol protected the cells against chloroacetaldehyde-induced cell death, although other nonthiol compounds and the antioxidative enzymes superoxide dismutase and catalase did not, suggesting that reactive oxygen species might not mediate cell death. In cells exposed to chloroacetaldehyde, levels of both total thiols and glutathione were significantly reduced. Chloroacetaldehyde also collapsed the mitochondrial membrane potential of these cells, induced the release of cytochrome c from mitochondria to the cytosol and significantly reduced cellular ATP levels during the course of death. The mitochondrial potential collapse was also prevented by thiol compounds. Flow cytometric analyses by means of annexin-V and propidium iodide double staining and immunofluorescence staining of active caspase-3 revealed that cells subjected to a lethal dose of chloroacetaldehyde displayed features characteristic of necrosis and that caspase-3 was not activated in response to chloroacetaldehyde. Taken together, these findings suggest that Saos-2 cells exposed to chloroacetaldehyde die by necrosis resulting from a decrease in intracellular thiols, disruption of the mitochondrial membrane potential and the depletion of cellular ATP.
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PMID:Necrotic pathway in human osteosarcoma Saos-2 cell death induced by chloroacetaldehyde. 1741 23

Emerging epidemiological data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetic encephalopathy, depression and anxiety. Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. Curcumin, a well-established phenolic antioxidant and anti-inflammatory molecule, is capable of playing an important role against amyloid and dendritic pathology and thus has neuroprotective properties. The aim of the present study was to explore the effect of curcumin (60 mg/kg; p.o.) on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107% and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione level and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus were increased by 112% and 94% respectively. Serum TNF-alpha, a marker for inflammation, was found to increase by 1100% in diabetic rats. Chronic treatment with curcumin (60 mg/kg; p.o.) significantly attenuated cognitive deficit, cholinergic dysfunction, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of cholinergic dysfunction, oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the potential of curcumin as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
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PMID:Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. 1782 93

Patients affected by medium-chain acyl-CoA dehydrogenase deficiency (MCADD) suffer from acute episodes of encephalopathy whose underlying mechanisms are poorly known. The present work investigated the in vitro effect of cis-4-decenoic acid (cDA), which accumulates in MCADD, on important parameters of oxidative stress in cerebral cortex of young rats. cDA markedly induced lipid peroxidation, as verified by the increased levels of spontaneous chemiluminescence and thiobarbituric acid-reactive substances. Furthermore, cDA significantly increased carbonyl formation and sulphydryl oxidation, which is indicative of protein oxidative damage, and promoted 2',7'-dihydrodichlorofluorescein oxidation. It was also observed that the non-enzymatic tissue antioxidant defenses were decreased by cDA, whereas the antioxidant enzyme activities catalase, superoxide dismutase and glutathione peroxidase were not altered. Moreover, cDA-induced lipid peroxidation and GSH reduction was totally blocked by free radical scavengers, suggesting that reactive species were involved in these effects. The data indicate that oxidative stress is induced by cDA in rat brain in vitro and that oxidative damage might be involved in the pathophysiology of the encephalopathy in MCADD.
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PMID:Oxidative stress induction by cis-4-decenoic acid: relevance for MCAD deficiency. 1798 55

Oxygen free radicals may cause tissue injury in perinatal asphyxia. We measured plasma and cerebrospinal fluid levels of malondialdehyde and plasma levels of glutathione peroxidase, catalase, and superoxide dismutase in 50 term newborns with perinatal asphyxia and eight newborns without asphyxia. Neonates with sepsis, major congenital malformations, and hemolytic disease were excluded. The levels of plasma and cerebrospinal fluid malondialdehyde, as well as of plasma glutathione peroxidase, catalase, and superoxide dismutase, were significantly higher in newborns with perinatal asphyxia, and demonstrated a progressive increase with greater severity of hypoxic ischemic encephalopathy. Higher levels of plasma and cerebrospinal fluid malondialdehyde and plasma catalase were documented in newborns who died from hypoxic ischemic encephalopathy, compared with those who survived, but no such difference was found in plasma levels of glutathione peroxidase and superoxide dismutase. The data of the present study suggest that, despite the increased activities of antioxidant enzymes in perinatal asphyxia, these neonates experience higher degrees of oxidative stress, as evidenced by increased levels of plasma and cerebrospinal fluid malondialdehyde. Hence, oxygen free radicals can be considered to play a significant role in the pathophysiology of perinatal asphyxia.
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PMID:Oxidative stress in perinatal asphyxia. 1827 52

3-Hydroxyisobutyric aciduria is an inherited metabolic disease caused by 3-hydroxyisobutyryl-CoA dehydrogenase deficiency. Tissue accumulation and high urinary excretion of 3-hydroxyisobutyric acid is the biochemical hallmark of this disorder. Clinical phenotype is heterogeneous and generally includes dysmorphic features, delayed motor development, profound mental impairment, and acute encephalopathy. Lactic acidemia is also found in the affected patients, indicating that mitochondrial dysfunction may be involved in the pathophysiology of this disorder. Therefore, the aim of the present work was to investigate the in vitro effect of 3-hydroxyisobutyric acid (0.1, 0.5 and 1mM) on essential enzymes of energy metabolism, namely the activities of the respiratory chain complexes I-V, total, cytosolic and mitochondrial creatine kinase and Na(+), K(+)-ATPase in cerebral cortex homogenates of 30-day-old rats. We also measured the rate of oxygen consumption in brain mitochondrial preparations in the presence of 3-hydroxyisobutyric acid. 3-Hydroxyisobutyric acid significantly reduced complex I-III (20%), without affecting the other activities of the electron transport chain. Furthermore, 3-hydroxyisobutyric acid did not change state III, state IV and the respiratory control ratio in the presence of glutamate/malate or succinate, suggesting that its effect on cellular respiration was weak. On the other hand, the activities of total and mitochondrial creatine kinase, but not cytosolic creatine kinase, were inhibited (30%) by 3-hydroxyisobutyric acid. We also observed that 3-hydroxyisobutyric acid-induced inhibition of mitochondrial creatine kinase activity was fully prevented by pre-incubation of the homogenates with reduced glutathione, alpha-tocopherol or the combination of superoxide dismutase plus catalase, suggesting that this inhibition was mediated by oxidation of essential thiol groups of the enzyme probably by superoxide, hydrogen peroxide and/or peroxyl radicals. It was also demonstrated that Na(+), K(+)-ATPase activity from synaptic plasma membranes was markedly suppressed (37%) by 3-hydroxyisobutyric acid and that this effect was prevented by alpha-tocopherol co-incubation implying that peroxyl radicals were probably involved in this action. Considering the importance of the affected enzyme activities for brain metabolism homeostasis and neurotransmision, it is suggested that increased tissue levels of 3-hydroxyisobutyric acid may contribute to the neurodegeneration of patients affected by 3-hydroxyisobutyric aciduria and possibly explain previous reports describing elevated production and excretion of lactate.
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PMID:Evidence that 3-hydroxyisobutyric acid inhibits key enzymes of energy metabolism in cerebral cortex of young rats. 1832 19

Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters in children suffering from neurological disorders. Thirty children (aged 3-12 years) with neurological disorders (cerebral palsy [n = 12], seizures [n = 11], and encephalopathy [n = 7]) were recruited in the study group. Sixty healthy children (aged 3-12 years) from similar socio-economic environments and not suffering from any chronic disease were taken as the controls. Blood lead levels and oxidant/antioxidant status were determined. Mean blood lead level was significantly higher while delta-aminolevulinic acid dehydratase (delta-ALAD) activity, a biomarker for lead exposure, was significantly lower in the study group as compared to the control group (P < 0.05 for each). Malondialdehyde (MDA) levels, an end-product of lipid peroxidation, were significantly higher while the antioxidant glutathione (GSH) levels were significantly lower in the study group as compared to the control group (P < 0.05 for each). Activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were significantly higher in the study group than those of the control group (P < 0.05 for each). There were significant negative correlations of blood lead levels with delta-ALAD (r = -0.35; P < 0.05) and GSH (r = -0.31; P < 0.05), and positive correlations with MDA (r = 0.37; P < 0.05), SOD (r = 0.53; P < 0.05), and CAT (r = 0.31; P < 0.05). In turn, delta-ALAD had significant negative correlations with MDA (r = -0.29; P < 0.05), SOD (r = -0.28; P < 0.05) and CAT (r = -0.34; P < 0.05), but positive correlation with GSH (r = 0.32; P < 0.05). Although a causal pathway can not be determined from the present study, our findings indicate lead-induced oxidative stress in blood of children with neurological disorders. Lead-induced oxidative stress as an underlying mechanism for neurological diseases in children warranted further investigation.
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PMID:Oxidative stress and neurological disorders in relation to blood lead levels in children. 1854 29

In vitro studies have shown unequivocally that bilirubin is an antioxidant. We hypothesized that bilirubin serves a physiological role of an antioxidant in vivo. To investigate the probable protective role of bilirubin in vivo, term babies with clinical jaundice were grouped into four categories-serum total bilirubin (STB) <160 mg/l, 160-200 mg/l, >200 mg/l, and kernicterus. Serum bilirubin, serum albumin, plasma glucose-6-phosphate dehydrogenase (G6PD), lipid peroxidation in blood cells, and reduced glutathione (GSH) content in whole blood were investigated. We also measured superoxide dismutase (SOD) and catalase in hemolysate and total plasma antioxidant capacity (TAC). Lipid peroxidation and antioxidant enzymes were significantly lower in babies with STB <200 mg/l compared to controls. TAC had a positive and MDA had a negative correlation with STB till 200 mg/l. However, TAC had a negative and MDA had a positive correlation with bilirubin >200 mg/l and in babies with bilirubin encephalopathy. Elevated levels of MDA, SOD, and catalase and significantly decreased levels of reduced glutathione and total antioxidant capacity were observed in STB >200 mg/l group. Antioxidant enzymes were also significantly inhibited in bilirubin encephalopathy babies. Post phototherapy, MDA production and antioxidant levels were significantly increased whilst total antioxidant capacity and reduced glutathione were significantly decreased compared to pre-phototherapy values. Exchange transfusion resulted in reduced oxidative stress in subjects with encephalopathy, whereas no significant difference was observed in other babies with STB >200 mg/l. Taken together, the present study propounds that bilirubin acts as a physiological antioxidant till 200 mg/l concentration in full-term normal neonates. It is conjectured that beyond 200 mg/l, it can no longer be considered physiologic. However, the cause of pathological jaundice needs to be identified and treated. The present data documents that phototherapy also induces oxidative stress.
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PMID:Evaluation of oxidant and antioxidant status in term neonates: a plausible protective role of bilirubin. 1856 Jul 65

Diabetic encephalopathy is characterized by impaired cognitive functions that involve neuronal damage triggered by glucose driven oxidative stress. The objective of the present study was to determine whether N-acetylcysteine (NAC) supplementation ameliorates learning and memory deficits caused by hyperglycemia-induced oxidative stress in experimental diabetes. Male Wistar rats (200-250 g) were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using elevated plus maze test after 8 weeks of induction of diabetes. Acetylcholinesterase activity, a marker of cholinergic function, was decreased by 15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of diabetic rats compared to control rats. There was an increase in lipid peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and total thiol content along with decrease in the activities of superoxide dismutase, catalase and glutathione reductase. However, glutathione peroxidase activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and brain stem respectively, while the activity of glutathione-s-transferase decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day in drinking water) significantly attenuated cognitive deficits and oxidative stress in diabetic rats. Our results emphasize the involvement of increased oxidative stress in cognitive impairment in diabetic animals and point towards the potential beneficial role of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
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PMID:Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes. 1880 43


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