The inhibition stage of lipid peroxidation during stress

Stress is shown to induce at first the generalized inhibition of lipid peroxidation (LPO), and then the activation of LPO. In brain and blood serum of rats subjected to continuous footshock as well as to restraint stress LPO products decreased and superoxide scavenging activity increased during the initial period of stress, after 1 hour of footshock LPO indices nearly reached normal values, and after 2 hours of footshock the accumulation of LPO products and decrease of superoxide scavenging activity were seen. LPO inhibition was accompanied by accumulation of easy oxidizable brain phospholipids and by depletion of brain cholesterol, during LPO activation brain cholesterol content and cholesterol-phospholipid ratio increased. The content of LPO products--fluorescent Schiff bases in blood plasma of women suffering from algomenorrhea at first decreased (O-12 h) and then dramatically increased (12-24 h) after a onset of pain at the beginning of menstruation. The data suggest that the stage of LPO inhibition precedes its activation during stress.     

Changes in rat brain monoamine turnover following chronic antidepressant administration

Changes in rat brain monoamine turnover were studied following the chronic administration of five agents which markedly differ in their patterns of monoamine uptake inhibition. Compounds (10 mg/kg, i.p.) were injected once daily for 14 days and experiments undertaken 24 h after the last injection. Chronic administration of desipramine or mianserin elevated brain MOPEG-SO₄ content and the α-MT-induced reduction in brain NA levels was enhanced by chronic desipramine. either antidepressant altered turnover of brain DA or 5-HT. Steady state levels of brain 5-HIAA or striatal levels of DOPAC or HVA were also unchanged. Chronically administered Org 6582, a selective inhibitor of 5-HT uptake, decreased basal and attenuated the probenecid-induced increase iin brain 5-HIAA levels. Chronic Org 6582 had no effect on NA or DA turnover and on the levels of MOPEG-SO₄, DOPAC or HVA. Neither maprotiline nor chlorimipramine altered turnover of NA, DA or 5-HT or levels of metabolites. Thus, in contrast to the acute situation, chronically administered desipramine increases rat brain NA turnover. Conversely, acute and chronic Org 6582 administration yield similar findings, viz. a decrease in turnover. These observations suggest that rat brain 5-HT systems are more resistant than NA systems to adaptive changes following a prolonged inhibition of monoamine uptake.     

Effects of Single and Repeated Footshock on Dopamine Release and Metabolism in the Brains of Fischer Rats

Abstract: Changes in the tissue levels of 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and dopamine in the frontal cortex, hypothalamus, nucleus accumbens, and striatum were evaluated after 0.5-4 h of footshock (2 mA, for 3 s every 30 ± 5 s) in Fischer rats. 3-MT, DOPAC, and HVA levels in the four brain areas peaked at 0.5 h and in most cases returned to baseline values within 4 h. No changes were found in dopamine levels. Repeated footshock stress was evaluated by administering 10 footshock sessions (0.5 h, two per day for 5 days). At the end of the 10th footshock session, 3-MT levels were higher than at the end of the first footshock session in three of the four brain regions, indicating sensitization of dopamine release. No differences were found between the first and 10th footshock sessions in DOPAC and HVA levels. Fourteen days after the 10th footshock session, the levels of 3-MT, DOPAC, and HVA were the same as in control rats in all four brain regions. A 0.5-h footshock challenge presented 14 days after the 10th footshock session attenuated DOPAC levels in the hypothalamus and nucleus accumbens. In contrast, DOPAC and HVA levels in the frontal cortex showed sensitization after footshock challenge, and a similar trend was apparent for 3-MT levels. These results indicate that repeated footshock stress induces generalized sensitization of dopamine release and turnover in some areas of the brain of Fischer rats. This sensitization may persist in the cortical but not subcortical dopamine neurons after discontinuation of the treatment.     

Chronic Stress Increases Serotonin and Noradrenaline in Rat Brain and Sensitizes Their Responses to a Further Acute Stress

The effects of 1 h/day restraint in plastic tubes for 24 days on the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan (TP), and noradrenaline (NA) in six regions of rat brain 20 h after the last restraint period were investigated. The levels of 5-HT, 5-HIAA, and NA but not TP increased in several regions. The effects of 1 h of immobilization on both control and chronically restrained rats were also studied. Immobilization per se did not alter brain 5-HT, 5-HIAA, and TP levels, but decreased NA in the pons plus medulla oblongata and hypothalamus. However, immobilization after chronic restraint decreased 5-HT, increased 5-HIAA, and decreased NA in most brain regions in comparison with values for the chronically restrained rats. We suggest that chronic restraint leads to compensatory increases of brain 5-HT and NA synthesis and sensitizes both monoaminergic systems to an additional acute stress. These changes may affect coping with stress demands.     

Brain Polyamine Stress Response: Recurrence After Repetitive Stressor and Inhibition by Lithium

Abstract: We recently demonstrated that, unlike in peripheral tissues, the increase in activity of polyamine synthesizing enzymes observed in the brain after acute stress can be prevented by long-term, but not by short-term, treatment with lithium. In the present study we sought to examine the effects of chronic intermittent stress on two key polyamine synthesizing enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase, and their modulation by lithium treatment. Adult male rats were subjected to 2 h of restraint stress once daily for 5 days and to an additional delayed stress episode 7 days later. Enzyme activities were assayed 6 h after the beginning of each stress episode. In contrast to the liver, where ornithine decarboxylase activity was increased (300% of the control) only after the first stress episode, the enzyme activity in the brain was increased after each stress episode (to ～170% of the control). Unlike ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity was slightly reduced after the first episode (86% of the control) but remained unchanged thereafter. After cessation of the intermittent stress period, an additional stress episode 7 days later led again to an increase in ornithine decarboxylase activity in the brain (225% of the control) but not in the liver, whereas S-adenosylmethionine decarboxylase activity remained unchanged. The latter increase in ornithine decarboxylase activity was blocked by lithium treatment during the intervening 7-day interval between stressors. The results warrant the following conclusions: (a) Repetitive application of stressors results in a recurrent increase in ornithine decarboxylase activity in the brain but to habituation of this response in the liver. (b) This brain polyamine stress response can be blocked by long-term (days) lithium treatment. (c) The study implicates an overreactive polyamine response as a component of the adaptive, or maladaptive, brain response to stressful events and as a novel molecular target for lithium action.     

The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.     

Acute Stress Increases Depolarization-Evoked Glutamate Release in the Rat Prefrontal/Frontal Cortex: The Dampening Action of Antidepressants

Background

Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.

Methodology/Findings

Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.

Conclusions/Significance

Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress, shown here for the first time, could be related to the therapeutic action of these drugs.     

Salicylic acid-induced changes to growth and phenolic metabolism in <Emphasis Type="Italic">Matricaria chamomilla</Emphasis> plants

The influence of salicylic acid (SA) doses of 50 and 250 μM, for a period of up to 7 days, on selected physiological aspects and the phenolic metabolism of Matricaria chamomilla plants was studied. SA exhibited both growth-promoting (50 μM) and growth-inhibiting (250 μM) properties, the latter being correlated with decrease of chlorophylls, water content and soluble proteins. In terms of phenolic metabolism, it seems that the higher SA dose has a toxic effect, based on the sharp increase in phenylalanine ammonia-lyase (PAL) activity (24 h after application), which is followed by an increase in total soluble phenolics, lignin accumulation and the majority of the 11 detected phenolic acids. Guaiacol-peroxidase activity was elevated throughout the experiment in 250 μM SA-treated plants. In turn, some responses can be explained by mechanisms associated with oxidative stress tolerance; these mitigate acute SA stress (which is indicated by an increase in malondialdehyde content). However, PAL activity decreased with prolonged exposure to SA, indicating its inhibition. Accumulation of coumarin-related compounds (umbelliferone and herniarin) was not affected by SA treatments, while (Z)- and (E)-2-β-d-glucopyranosyloxy-4-methoxycinnamic acids increased in the 250 μM SA-treated rosettes. Free SA content in the rosettes increased significantly only in the 250 μM SA treatment, with levels tending to decrease towards the end of the experiment and the opposite trend was observed in the roots.     

The physiological performance and immune responses of juvenile Amur sturgeon (Acipenser schrenckii) to stocking density and hypoxia stress

Stocking density and hypoxia are considered priority issues in aquaculture research. In this study, two experiments were carried out in order to investigate the effects of chronic stress (stocking density) and acute stress (hypoxia) on the immune physiology responses (hematology, serum cortisol, glucose, total protein and the mRNA expression of CYP 1A) of juvenile Amur sturgeon (Acipenser schrenckii). In the chronic stress study, three triplicate groups of Amur sturgeon (42.0 ± 2.3 g) were reared in nine square concrete ponds (4.4 × 4.4 × 0.45 m³) at three stocking densities (3.7, 6.9 and 9.0 kg/m³) for 50 days. In the acute stress study, three triplicate groups: normal group (7 mg/l), hypoxia group 1 (5 mg/l) and hypoxia group 2 (3 mg/l) were used in nine 100 L indoor tanks. Sampling was performed at the end of the stocking density experiment (50 days) and at 0, 0.5, 1.5, 3 and 6 h after hypoxia stress. The results showed that increased stocking density reduced the morphological indexes (hepatosomatic index, spleen-somatic index and kidney-somatic index), while total protein and hemoglobin increased significantly in the stressed group. In response to hypoxia, the levels of cortisol, glucose and hematological parameters elevated significantly after this stress. As for spleen-somatic index, there was a decline after hypoxia though H1 group returned to the normal level at 3 h and 6 h after hypoxia stress. Additionally, In order to better understand the immune response of Amur sturgeon to chronic and acute stressors, we cloned the complete coding sequence of Amur sturgeon CYP 1A for the first time and investigated its tissue-specific expression and stress-induced expression. CYP 1A mRNA in liver showed over expressions both in crowding condition and in hypoxia stress. The same trend was also found in spleen and kidney which may provide evidence that CYP 1A could serve as a good indicator of immune response in Amur sturgeon. In addition, the result suggested a typical immune response both in high stocking density and hypoxia stress. But the chronically stressed fish might have an adaptation capability to survive under a stable crowding condition without a change in some immune parameters (cortisol, glucose, WBCs and RBCs).     

Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15–21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male–female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.     

Mechanisms and Significance of the Increased Brain Uptake of Tryptophan

Changes in brain tryptophan concentrations may affect the synthesis of brain serotonin (5-hydroxytryptamine, 5-HT). Concentrations of tryptophan are regulated more than those of any other amino acid. Such stimuli as acute stress, carbohydrate ingestion, and treatment with various drugs increase the brain content of tryptophan. Treatment of rats and mice with interleukin-1 (IL-1), interleukin-6 (IL-6), lipopolysaccharide (LPS), and β-adrenoceptor agonists, as well as a variety of stressors, such as footshock and restraint, all increase brain concentrations of tryptophan. The peak effect following both acute stress and β-adrenoceptor agonist administration occurs within 30–60 min, whereas the peak effect following LPS and the cytokines occurs much later at around 4–8 h. Experiments using the ganglionic blocker chlorisondamine, and β-adrenoceptor antagonists suggest that the sympathetic nervous system plays an important role in the modulation of brain tryptophan concentrations. The mechanisms involved in the increases observed in brain tryptophan are discussed, as well as their possible biological significance. Special issue dedicated to Dr. Simo S. Oja     

Acute Restraint-Mediated Increases in Glutamate Levels in the Rat Brain: An In Vivo <Superscript>1</Superscript>H-MRS Study at 4.7 T

It is well known that a variety of stressors induces a significant alteration in various putative neurotransmitters in the mammalian CNS. However, relatively little attention has been paid on the alteration of central glutamate neurotransmission, which is a major excitatory neurotransmitter in the brain. The present study aimed to determine whether acute restraint stress induces the changes in neurotransmitter level, especially glutamate, in rat brain and to examine whether 1-h recovery time after the termination of stress can revert to its pre-stress state. In vivo ¹H-NMR spectra were acquired from the cerebral cortex and hippocampus (control: N = 10, stress: N = 10, stress + 1 h rest: N = 10) immediately or after 1 h rest from restraint stress. All in vivo proton spectra were automatically analyzed using LCModel. We found that acute restraint stress induced significant increase in glutamate concentrations in the cerebral cortex and the hippocampus of rat. However, the level could not revert to its pre-stress state by the end of 1-h recovery period in cerebral cortex of rats. In addition, glutamine/glutamate ratio, which may function as an index of the glutamatergic neurotransmission, was significantly lower in the cerebral cortex of both stress and 1 h stress + 1 h recovery groups, as compared to control. Our finding may provide important evidence for altered glutamatergic activity after the stress and suggest a potential biochemical marker for eventual diagnosis and/or therapy monitoring in mood disorder.     

Restraint Stress in Rats Alters Gene Transcription and Protein Translation in the Hippocampus

Stress is a relatively new and emerging risk factor for Alzheimer’s disease (AD). Severe stress can alter brain characteristics such as neuronal plasticity, due to changes in the metabolism of cytoskeletal proteins. In this study, male Wistar rats were exposed to restraint stress (RS) for 5 h daily for different time periods. At the end of the exposure periods, the amounts of β-actin, cofilin, amyloid precursor protein (APP) and mitogen-activated protein kinase 1 (MAPK-1) RNAs and proteins were investigated. The mRNA expressions of β-actin, cofilin and MAPK-1 followed U-shaped time course. Acute (3 days) and chronic (21 days) RS caused a fourfold and tenfold increases, respectively, in hippocampal β-actin mRNA expression. In the case of cofilin mRNA expression, elevations were detected in the hippocampus on days 3, 7 and 21. The APP mRNA level was increased on day 21. On protein level, chronic stress elevated the levels of β-actin, cofilin and APP in the hippocampus. These results suggest that stress causes the induction of some genes and proteins that are also elevated in AD selectively in the hippocampal region of the rat brain.     

Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain

Brain hypoxiainduces an increase in brain vascularity, presumably mediated byvascular endothelial growth factor (VEGF), but it is unclear whetherVEGF is required to maintain the increase. In these studies, brain VEGFmRNA and protein levels were measured in adult mice kept in hypobaricchambers at 0.5 atm for 0, 0.5, 1, 2, 4, 7, and 21 days. Hypoxia wasaccompanied by a transient increase of VEGF mRNA expression: twofold by0.5 day and a maximum of fivefold by 2 days; these were followed by adecrease at 4 days and a return to basal levels by 7-21 days. VEGFprotein expression induced by hypoxia was bimodal, initiallyparalleling VEGF mRNA. There was an initial small increase at 12 h thatreached a maximum by day 2, and, aftera transient decrease on day 4, theprotein expression increased again on day7 before it returned to normoxic levels after 21 days.Thus, despite continued hypoxia, both VEGF mRNA and protein levelsreturned to basal after 7 days. These data suggest a metabolicnegative-feedback system for VEGF expression during prolonged hypoxiain the brain.

     

Effects of Hypoxia on the Activities of Noradrenergic and Dopaminergic Neurons in the Rat Brain

The effects of hypoxia (10% O2, 90% N2) on the content, biosynthesis, and turnover of noradrenaline (NA) and 3,4-dihydroxyphenylethylamine (dopamine, DA) in the rat brain were examined. Up to 24 h following exposure to hypoxia, NA content in the whole brain was decreased, whereas DA content remained unchanged. The accumulation of 3,4-dihydroxyphenylalanine (DOPA) after central decarboxylase inhibition was decreased. The turnover rate of DA after synthesis inhibition was markedly decreased up to 8 h and returned to the control level within 24 h. In contrast, the turnover rate of NA was all but unchanged, except for a 4-h exposure. The 2-h exposure to the hypoxic environment resulted in a significant decrease in NA content and DOPA accumulation in all brain regions tested, but no significant change was observed in DA content. The turnover rate of DA was remarkably decreased in all brain regions tested, whereas the rate of NA was slightly decreased only in the cerebral cortex and hippocampus. These results suggest that although hypoxia decreases the biosynthesis of both NA and DA, the effects of oxygen depletion on the functional activities of NA neurons differ considerably from those of DA neurons: Only in the cerebral cortex and hippocampus are the NA neurons slightly sensitive to hypoxia, whereas the DA neurons are most sensitive in all brain regions.     

Dynamic Pattern of Gene Expression of ZnT-4, Caspase-3, LC3, and PRG-3 in Rat Cerebral Cortex Following Flurothyl-Induced Recurrent Neonatal Seizures

Zinc transporters, plasticity-related genes, and autophagic/apoptotic pathway both are associated with developmental seizure-induced brain excitotoxicity. Here, for the first time, we report the timing of expression pattern of zinc transporter 4 (ZnT-4), plasticity-related gene 3 (PRG-3), specific marker of autophagic vacuoles (LC3), and apoptotic marker caspase-3 in cerebral cortex following neonatal seizures. A seizure was induced by inhalant flurothyl daily in neonatal Sprague–Dawley rats from postnatal day 6 (P6). Rats were assigned into the recurrent-seizure group (RS, seizures induced in six consecutive days) and the control group. At 1.5 h, 3 h, 6 h, 12 h, 24 h, 48 h, 7 days, and 14 days after the last seizure, the mRNA level of the four genes in cerebral cortex was detected using RT–PCR method. At an early period 6 h or 12 h after the last seizures, both ZnT-4 and LC3 showed significantly up-regulated mRNA level while PRG-3 showed significantly down-regulated mRNA level at 12 h in cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 7 days after the last seizure, the mRNA level of caspase-3 down-regulated; meanwhile, there was up-regulated mRNA level of LC-3 in RS group when compared to the control rats. This is the first report investigating the gene expression pattern of ZnT-4, PRG-3, LC-3, and caspase-3 in the developing brain. The results suggest that the disturbed expression pattern of the four genes might play a role in the pathophysiology of recurrent neonatal seizure-induced acute and long-term brain damage.     

β-Lapachone Induces Acute Oxidative Stress in Rat Primary Astrocyte Cultures that is Terminated by the NQO1-Inhibitor Dicoumarol

β-lapachone (β-lap) is reduced in tumor cells by the enzyme NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1) to a labile hydroquinone which spontaneously reoxidises to β-lap, thereby generating reactive oxygen species (ROS) and oxidative stress. To test for the consequences of an acute exposure of brain cells to β-lap, cultured primary rat astrocytes were incubated with β-lap for up to 4 h. The presence of β-lap in concentrations of up to 10 µM had no detectable adverse consequences, while higher concentrations of β-lap compromised the cell viability and the metabolism of astrocytes in a concentration- and time-dependent manner with half-maximal effects observed for around 15 µM β-lap after a 4 h incubation. Exposure of astrocytes to β-lap caused already within 5 min a severe increase in the cellular production of ROS as well as a rapid oxidation of glutathione (GSH) to glutathione disulfide (GSSG). The transient cellular accumulation of GSSG was followed by GSSG export. The β-lap-induced ROS production and GSSG accumulation were completely prevented in the presence of the NQO1 inhibitor dicoumarol. In addition, application of dicoumarol to β-lap-exposed astrocytes caused rapid regeneration of the normal high cellular GSH to GSSG ratio. These results demonstrate that application of β-lap to cultured astrocytes causes acute oxidative stress that depends on the activity of NQO1. The sequential application of β-lap and dicoumarol to rapidly induce and terminate oxidative stress, respectively, is a suitable experimental paradigm to study consequences of a defined period of acute oxidative stress in NQO1-expressing cells.

     

Decreased glutamine synthetase,increased citrulline–nitric oxide cycle activities,and oxidative stress in different regions of brain in epilepsy rat model

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.