Estradiol Protects Against Oxidative Stress Induced by Chronic Variate Stress

Neurochemical gender-specific effects have been observed following chronic stress. The aim of this study was to verify the effects of chronic variable stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in three distinct structures of brain: hippocampus, cerebral cortex and hypothalamus of female rats, and to evaluate whether the replacement with estradiol in female rats exerts neuroprotection against oxidative stress. Results demonstrate that chronic stress had a structure-specific effect upon lipid peroxidation, since TBARS increased in hypothalamus homogenates of stressed animals, without alterations in the other structures analyzed. Estradiol replacement was able to counteract this effect. In hippocampus, estradiol induced a significant increase in TAR. No differences in DCF levels were observed. In conclusion, the hypothalamus is more susceptible to oxidative stress in female rats submitted to chronic variable stress, and this effect is prevented by estradiol treatment.     

Repeated Restraint Stress Induces Oxidative Damage in Rat Hippocampus

It has been shown that emotional stress may induce oxidative damage, and considerably change the balance between pro-oxidant and antioxidant factors in the brain. The aim of this study was to verify the effect of repeated restraint stress (RRS; 1 h/day during 40 days) on several parameters of oxidative stress in the hippocampus of adult Wistar rats. We evaluated the lipid peroxide levels (assessed by TBARS levels), the production of free radicals (evaluated by the DCF test), the total radical-trapping potential (TRAP) and the total antioxidant reactivity (TAR) levels, and antioxidant enzyme activities (SOD, GPx and CAT) in hippocampus of rats. The results showed that RRS induced an increase in TBARS levels and in GPx activity, while TAR was reduced. We concluded that RRS induces oxidative stress in the rat hippocampus, and that these alterations may contribute to the deleterious effects observed after prolonged stress.     

Gender differences in oxidative stress in spinal cord of rats submitted to repeated restraint stress

Behavioral and neurochemical gender-specific effects have been observed following repeated stress. The aim of this study is to verify the effects of repeated restraint stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in the spinal cord of male and female rats. Results demonstrate no effect on lipoperoxidation; chronic stress decreased TAR both in male and female spinal cord. In addition, gender differences were observed both in TAR and in the production of free radicals, both being increased in females. These results may be relevant to the gender-specific differences observed after exposure to repeated stress.     

Effect of Chronic Variate Stress on Thiobarbituric-Acid Reactive Species and on Total Radical-Trapping Potential in Distinct Regions of Rat Brain

It has been suggested that oxidative stress is involved in aging and neuropathologic disorders. In addition, chronic stress and high corticosterone levels are suggested to induce neuronal death. The aim of this study is to verify the effect of chronic variate stress on lipoperoxidation and on the total radical-trapping potential (TRAP) in hippocampus, hypothalamus and cerebral cortex. Adult male Wistar rats were submitted to different stressors during 40 days. Lipid peroxide levels were assessed by the thiobarbituric acid reactive species (TBARS) reaction, and TRAP was measured by the decrease in luminescence using the 2-2-azo-bis(2-amidinopropane)-luminol system. The results showed that in cerebral cortex homogenates chronic stress induces an increase in oxidative stress. In hypothalamus a decreased lipoperoxidation was observed, however TRAP showed no difference. In hippocampus no difference was observed. We concluded that prolonged stress induces oxidative stress which varies selectively with the brain region.     

Hypobaric hypoxia induces oxidative stress in rat brain

High altitude exposure results in decreased partial pressure of oxygen and an increased formation of reactive oxygen and nitrogen species (RONS), which causes oxidative damage to lipids, proteins and DNA. Exposure to high altitude appears to decrease the activity and effectiveness of antioxidant enzyme system. The antioxidant system is very less in brain tissue and is very much susceptible to hypoxic stress. The aim of the present study was to investigate the time dependent and region specific changes in cortex, hippocampus and striatum on oxidative stress markers on chronic exposure to hypobaric hypoxia. The rats were exposed to simulated high altitude equivalent to 6100 m in animal decompression chamber for 3 and 7 days. Results indicate an increase in oxidative stress as seen by increase in free radical production, nitric oxide level, lipid peroxidation and lactate dehydrogenase levels. The magnitude of increase in oxidative stress was more in 7 days exposure group as compared to 3 days exposure group. The antioxidant defence system such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) levels were significantly decreased in all the three regions. The observation suggests that the hippocampus is more susceptible to hypoxia than the cortex and striatum. It may be concluded that hypoxia differentially affects the antioxidant status in the cortex, hippocampus and striatum.     

Acute and Chronic Hyperammonemia Modulate Antioxidant Enzymes Differently in Cerebral Cortex and Cerebellum

Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 × 10³ & 8 × 10³ μmol/kg b.w. at 30 min interval for acute and 8 × 10³ μmol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01–0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by ∼ 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA.     

Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats

The aging process is associated with cognitive impairment and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress. We determined some parameters of oxidative stress in homogenates of hippocampus, hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A significant age-dependent increase in the generation of free radicals was observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx) activity was significantly reduced in hypothalamus and hippocampus from 6-months-old rats; a decline on GPx and catalase activities in adrenal glands of 24-months-old animals was also present. Interestingly, a great decrease in total antioxidant capacity was found in all tissues tested. Reported findings support the idea that oxidative events participate on multiple neuroendocrine-metabolic impairments and suggest that the oxidative stress found in hippocampus, hypothalamus and adrenals might be associated with age-related physiological deficits.     

Effect of Chronic Administration of the Vinyl Chalcogenide 3-Methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on Oxidative Stress in Different Brain Areas of Rats

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 μg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.     

Induction of Oxidative Stress by Chronic and Acute Glutaric Acid Administration to Rats

1. Glutaric acidemia type I (GA I) is a neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which leads to tissue accumulation of predominantly glutaric acid (GA) and also 3-hydroxyglutaric acid to a lesser amount. Affected patients usually present progressive cortical atrophy and acute striatal degeneration attributed to the toxic accumulating metabolites. 2. In the present study, we determined a number of oxidative stress parameters, namely chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), glutathione (GSH) levels, and the activities of catalase and glutathione peroxidase (GPx), in various tissues from rats chronically exposed to GA or to saline (controls). High GA concentrations, similar to those found in glutaric aciduria type I, were induced in the brain by three daily subcutaneous injections of saline-buffered GA (5 μmol/g body weight) to Wistar rats of 5–22 days of life. The parameters were assessed 12 h after the last GA administration in different brain structures, skeletal muscle, heart, liver, erythrocytes, and plasma. The lipid peroxidation parameters chemiluminescence and/or TBA-RS measurements were found significantly increased in midbrain, liver, and erythrocytes of GA-injected rats. The activity of GPx was significantly reduced in midbrain and markedly increased in liver. TAR measurement was significantly reduced in midbrain and liver. Furthermore, GSH levels were reduced in liver and heart. We also investigated the acute in vivo effect of GA administration on the same oxidative stress parameters in cerebral structures and erythrocytes from 22-day-old rats. We found that TBA-RS values were significantly increased in erythrocytes, TAR levels were markedly decreased in midbrain and cerebellum, and GPx activity mildly reduced in the midbrain. 3. These data showing an imbalance between antioxidant defences and oxidative damage, particularly in midbrain, liver, and erythrocytes from GA-injected rats, indicate that oxidative stress might be involved in GA toxicity and that the midbrain, where the striatum is located, is the brain structure more susceptible to GA chronic and acute exposition.     

The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism

Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.     

The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism

Abstract

Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.     

Interactions Between Chronic Stress and Chronic Consumption of Caffeine on the Enzymatic Antioxidant System

We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.     

Chronic Stress and Lithium Treatments Alter Hippocampal Glutamate Uptake and Release in the Rat and Potentiate Necrotic Cellular Death After Oxygen and Glucose Deprivation

This study was undertaken to evaluate the effects of chronic variate stress and lithium treatment on glutamatergic activity and neuronal vulnerability of rat hippocampus. Male Wistar rats were simultaneously treated with lithium and submitted to a chronic variate stress protocol during 40?days, and afterwards the hippocampal glutamatergic uptake and release, measured in slices and synaptosomes, were evaluated. We observed an increased synaptosomal [(3)H]glutamate uptake and an increase in [(3)H]glutamate stimulated release in hippocampus of lithium-treated rats. Chronic stress increased basal [(3)H]glutamate release by synaptosomes, and decreased [(3)H]glutamate uptake in hippocampal slices. When evaluating cellular vulnerability, both stress and lithium increased cellular death after oxygen and glucose deprivation (OGD). We suggest that the manipulation of glutamatergic activity induced by stress may be in part responsible for the neuroendangerment observed after stress exposure, and that, in spite of the described neuroprotective effects of lithium, it increased the neuronal vulnerability after OGD.     

Malathion-induced Oxidative Stress in Rat Brain Regions

Malathion is a pesticide with high potential for human exposure. However, it is possible that during the malathion metabolism, there is generation of reactive oxygen species (ROS) and malathion may produce oxidative stress in intoxicated rats. The present study was therefore undertaken to determine malathion-induced lipid peroxidation (LPO), protein carbonylation and to determine whether malathion intoxication alters the antioxidant system in brain rats. Malathion was administered intraperitoneally in the acute and chronic protocols in the doses of 25, 50, 100 and 150 mg malathion/kg. The results showed that LPO in brain increased in both protocols. The increased oxidative stress resulted in an increased in the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), observed in cortex, striatum in the acute malathion protocol and hippocampus in the chronic malathion protocol. Our results demonstrated that malathion induced oxidative stress and modulated SOD and CAT activity in selective brain regions.     

Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats.     

Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures

Chronic variate stress was seen to decrease the ingestion of sweet food when compared to control rats. Brain monoamines are known to be involved in the control of food intake, serotonin appears to be involved in the mechanisms of satiety, and dopamine in mediating appetite or approach behaviors triggered by incentive stimuli associated with rewards. The effect of chronic variate stress on cerebral levels of monoamines was also studied in rats. Increased levels of DOPAC were observed in the frontal cortex and in the hippocampus and an increased 5-HIAA/5-HT ratio was also observed in this latter structure. In the hypothalamus, levels of HVA and DOPAC were decreased, as well as the DOPAC/DA ratio, while no difference was found in amygdala. During the treatment, there were no differences in the consumption of water and regular food between stressed and control animals. An increase in the adrenal weight was observed at the end of the treatment. The results suggest that emotional changes, such as exposure to stress situations can influence feeding behavior, chronic variate stress causes decreased ingestion of sweet food and decreased dopaminergic neurotransmission in hypothalamus. Increased dopamine metabolite levels in the cortex and hippocampus were also observed and some of these modifications may be related to alterations in feeding behavior.     

Antioxidant responses to chronic hypoxia in the rat cerebellum and pons

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and sleep fragmentation and deprivation. Exposure to CIH results in oxidative stress in the cortex, hippocampus and basal forebrain of rats and mice. We show that sustained and intermittent hypoxia induces antioxidant responses, an indicator of oxidative stress, in the rat cerebellum and pons. Increased glutathione reductase (GR) activity and thiobarbituric acid reactive substance (TBARS) levels were observed in the pons and cerebellum of rats exposed to CIH or chronic sustained hypoxia (CSH) compared with room air (RA) controls. Exposure to CIH or CSH increased GR activity in the pons, while exposure to CSH increased the level of TBARS in the cerebellum. The level of TBARS was increased to a greater extent after exposure to CSH than to CIH in the cerebellum and pons. Increased superoxide dismutase activity (SOD) and decreased total glutathione (GSHt) levels were observed after exposure to CIH compared with CSH only in the pons. We have previously shown that prolonged sleep deprivation decreased SOD activity in the rat hippocampus and brainstem, without affecting the cerebellum, cortex or hypothalamus. We therefore conclude that sleep deprivation and hypoxia differentially affect antioxidant responses in different brain regions.     

Sleep deprivation under sustained hypoxia protects against oxidative stress

We previously showed that total sleep deprivation increased antioxidant responses in several rat brain regions. We also reported that chronic hypoxia enhanced antioxidant responses and increased oxidative stress in rat cerebellum and pons, relative to normoxic conditions. In the current study, we examined the interaction between these two parameters (sleep and hypoxia). We exposed rats to total sleep deprivation under sustained hypoxia (SDSH) and compared changes in antioxidant responses and oxidative stress markers in the neocortex, hippocampus, brainstem, and cerebellum to those in control animals left undisturbed under either sustained hypoxia (UCSH) or normoxia (UCN). We measured changes in total nitrite levels as an indicator of nitric oxide (NO) production, superoxide dismutase (SOD) activity and total glutathione (GSHt) levels as markers of antioxidant responses, and levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls as signs of lipid and protein oxidation products, respectively. We found that acute (6h) SDSH increased NO production in the hippocampus and increased GSHt levels in the neocortex, brainstem, and cerebellum while decreasing hippocampal lipid oxidation. Additionally, we observed increased hexokinase activity in the neocortex of SDSH rats compared to UCSH rats, suggesting that elevated glucose metabolism may be one potential source of the enhanced free radicals produced in this brain region. We conclude that short-term insomnia under hypoxia may serve as an adaptive response to prevent oxidative stress.     

Oxidative stress is closely related to clinical severity of pre-eclampsia

Pre-eclampsia is a hypertensive disorder of pregnancy in which enzymatic antioxidant defenses fail and tissues are injured. This prospective case-control study evaluated whether pre-eclamptic women and their newborns show higher degrees of oxidative stress than normal pregnancies and sought to determine if this stress is related to clinical severity. Forty-four pre-eclamptic and thirty healthy pregnant women attending two hospitals in Valparaíso, Chile, were studied. The following plasmatic variables of antioxidant capacity were evaluated: glutathione peroxidase activity (GPx), total antioxidant capacity measured by oxidation of ABTS substrate (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), and superoxide dismutase activity (SOD). malondialdehide (MDA) was measured to evaluate lipoperoxidation. The evaluation was performed at diagnosis of pre-eclampsia, delivery, 30 days and 120 days post delivery. Newborns were studied at delivery through umbilical cord blood samples. Our analysis shows that antioxidant enzyme activity (SOD, GPx, ABTS) was significantly decreased, while lipoperoxidation (MDA) was increased in both pre-eclamptic groups compared to normal pregnant women (p<0.01). Statistically significant difference was found between mild and severe pre-eclamptic groups (p<0.01), for all biochemical markers studied. Therefore, the clinical severity of this pathology is closely related to the degree of oxidative stress.