Aysel Agar

THE EFFECT OF CHRONIC RESTRAINT STRESS ON SPATIAL LEARNING AND MEMORY: RELATION TO OXIDANT STRESS

The aim of this study was to investigate the effect of chronic restraint stress (RS) on spatial learning and memory. Fifty healthy male Wistar rats, aged three months were used. They were equally divided into five groups—C: Control, W: Water Maze, CS-1: Restrained for 21 days (1 h/day) + water maze protocol following stress period, CS-2: Restrained for 28 days (1 h/day) + water maze protocol during last 7 days of stress period, CS-3: Restrained for 21 days and allowed to recovery for 7 days (1 h/day). Corticosterone levels were higher in all stress groups than in C and W groups. Nitrite levels of frontal cortex and hippocampus were found to be elevated in chronic stress groups with respect to C and W groups. Thiobarbituric acid reactive substances (TBARS) of both tissues were increased significantly in CS1 and CS2 groups compared with C, W, and CS3 groups. Escape latencies of CS1 and CS2 groups were longer than those of the W group on each day of acquisition. In transfer test, CS1 and CS2 groups stayed significantly shorter in target quadrant according to the W group. Significant correlations between corticosterone and either nitrite or TBARS of hippocampus and frontal cortex were found. Both acquisition and memory performances were negatively correlated with plasma corticosterone level, nitrite, and TBARS levels of hippocampus and frontal cortex. The results of this study suggest that stress-induced lipid peroxidation may affect the acquisition and memory performances.

Influences of different stress models on the antioxidant status and lipid peroxidation in rat erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 - 2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Parkinsons disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases.

The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease.

This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the oxidative stress that occurs in an experimental mouse model of Parkinsons disease (PD). An experimental model of PD was created by four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 × 20 mg/kg, at 12h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36 mg/kg/day). The motor activity of the mice was evaluated via the pole test, and the dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant enzymes in the brain were determined by spectrophotometric assays and the concentration of thiobarbituric acid-reactive substances (TBARS) were measured as an index of oxidative damage. The number of apoptotic dopaminergic cells significantly increased in MPTP-treated mice compared to controls. Although DHA significantly diminished the number of cell deaths in MPTP-treated mice, it did not improve the decreased motor activity observed in the experimental PD model. Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP+DHA group as compared to the MPTP group. TBARS levels in the brain were significantly increased following MPTP treatment. Glutathione peroxidase (GPx) and catalase (CAT) activities of brain were unaltered in all groups. The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group, but DHA treatment did not have an effect on SOD activity in the MPTP+DHA group. Our current data show that DHA treatment exerts neuroprotective actions on an experimental mouse model of PD. There was a decrease tendency in brain lipid oxidation of MPTP mice but it did not significantly.

Effect of alpha-lipoic acid on visual evoked potentials in rats exposed to sulfite

This study aimed to investigate the effect of alpha-lipoic acid (LA) administration on sulfite-induced alterations in visual evoked potentials (VEPs). Fifty two male albino Wistar rats were randomized into four experimental groups as follows; control (C), LA treated (L), sodium metabisulfite (Na(2)S(2)O(5)) treated (S), Na(2)S(2)O(5)+LA treated (SL). Na(2)S(2)O(5) (260 mg/kg/day) and LA (100 mg/kg/day) were given by intragastric intubation for 5 weeks. The latencies of VEP components were significantly prolonged in the S group and returned to control levels following LA administration. Thiobarbituric acid reactive substances (TBARS) levels in the S group were significantly higher than those detected in controls. LA significantly decreased brain and retina TBARS levels in the SL group compared with the S group. Sulfite caused a significant decrease in retina and brain glutathione peroxidase (GPx) activities which was restored to control levels via LA administration. Brain glutathione (GSH):glutathione disulfide (GSSG) ratio was significantly increased in rats jointly treated with sulfite and LA compared to rats treated with sulfite alone. Though not significant, a similar increase in GSH:GSSG ratio was also observed in the retina of SL group. This study showed that LA is protective against sulfite-induced VEP alterations and oxidative stress in the brain and retina.

Visual evoked potentials and optic nerve histopathology in normal and diabetic rats and effect of ginkgo biloba extract

Abstract. The purpose of this study was to test the possible therapeutic role of ginkgo biloba extract on the impairment of visual function and pathological histology of the optic nerve caused by early diabetes. Ginkgo biloba extract entraps oxygenated free radicals and is also a strong inhibitor of the platelet activation factor (PAF). For this purpose, VEP recordings and optic nerve histopathology were studied on alloxan diabetic and normal Swiss albino rats in four experimental groups. The VEP recordings showed no statistical significance between diabetic and normal rats. However, the amplitudes were significantly increased in diabetic animals with ginkgo biloba extract compared with the diabetics, supposing an impression of axonal protection. But the amplitude values were decreased in normal rats treated with the same extract compared with normal animals, assuming a toxic activity. Optic nerve ultrastructural findings also confirmed these VEP changes. It was concluded that this extract could be encouraging for human clinical trials of diabetes.

The effect of sulfite and chronic restraint stress on brain lipid peroxidation and anti-oxidant enzyme activities

Sulfites are used as anti-microbial and anti-oxidant agents in a variety of drugs, and function as a preservative in many food preparations. In addition to these effects, sulfites oxidize to sulfite radicals initiating lipid peroxidation. The objective of our study was to investigate the effect of restraint stress and sulfite on brain lipid peroxidation and anti-oxidant enzyme activities. Forty male Wistar rats, aged three months, were randomized to one of the following groups: control, restraint stress, sulfite-treated and restraint stress-/sulfite-treated. Chronic restraint stress was applied for 21 days (1 h/day) and sodium metabisulfite (520 mg/kg per day) was given by gavage for the same period. Lipid peroxidation was measured using the thiobarbituric acid (TBA) fluorometric assay. TBA-reactive substances (TBARS) were found increased in all treatment groups when compared to the control group. Spectrophotometric measurement of copper/zinc superoxide dismutase (Cu/Zn SOD) and catalase (CAT) revealed decreased enzyme activities in rats exposed to restraint stress compared to control and sulfite-treated rats. GSH-Px activities were significantly decreased in the restraint stress and sulfite-treated rats compared with the control rats. GSH-Px activity measured in restraint stress-/sulfite-treated rats was significantly lower than in the other groups. The presented data confirms the pro-oxidant activity of restraint stress and establishes that decreased anti-oxidant enzyme activities in restraint stress-treated rats enhances brain lipid peroxidation caused via the ingestion of sulfites.

Age-related changes in antioxidant enzyme activities and lipid peroxidation in lungs of control and sulfur dioxide exposed rats

Antioxidant defenses within the lung are pivotal in preventing damage from oxidative toxicants. There have also been several reports with conflicting results on the antioxidant system during aging. In this study, we attempted to investigate age-related alterations in both antioxidant enzyme activities and thiobarbituric acid-reactive substances (TBARS), a product of lipid peroxidation, in the whole lung of control and sulfur dioxide (SO2) exposed rats of different age groups (3-, 12-, and 24-months-old). Swiss-Albino Male rats were exposed to 10 ppm SO2 1 hr/day, 7 days/week for 6 weeks. The antioxidant enzymes examined include Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). A mixed pattern of age-associated alterations in antioxidant activities was observed. SOD, GSH-Px and GST activities were increased with age, but CAT activity was decreased. Lung SOD, GSH-Px and GST activities were also increased in response to SO2. The level of TBARS was increased with age. SO2 exposure stimulated lipid peroxide formation in the lung as indicated by an increase in the level of TBARS. These findings suggest that both aging and SO2 exposure may impose an oxidative stress to the body. We conclude that the increase in the activities of the antioxidant enzymes of the lung during aging, could be interpreted as a positive feedback mechanism in response to rising lipid peroxidation.

Effect of aminoguanidine on visual evoked potentials (VEPs), antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress

The purpose of the study was to investigate the effect of aminoguanidine (AG) on visual evoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), the activities of Cu, Zn superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and nitrite/nitrate levels. Forty healthy male Wistar rats, aged 3 months, were divided into four equal groups: Control (C), the group treated with aminoguanidine (A), the group exposed to restraint stress (S), the group exposed to restraint stress and treated with aminoguanidine (AS). Chronic restraint stress was applied for 21 days (1 h/day) and aminoguanidine (50 mg/kg/day) was injected intraperitoneally to the A and AS groups for the same period. Aminoguanidine treatment significantly decreased retina and brain TBARS levels in rats exposed to restraint stress compared to rats exposed to restraint stress alone. Aminoguanidine treatment produced a significant decrease in brain and retina nitrite and nitrate levels with respect to the control groups. Aminoguanidine increased all antioxidant enzyme activities in both brain and retina in rats exposed to restraint stress compared to rats exposed to restraint stress alone. All VEP components were significantly decreased in AG treated rats exposed to restraint stress compared to rats exposed to restraint stress alone. Our study clearly showed that AG has the potential to prevent changes caused by stress.

The effect of different hypertension models on active avoidance learning

This study tested the effects of different hypertension models on active avoidance learning in rats. Three-month-old male Wistar rats were divided randomly into six groups as follows: control (C), sham operated (sham), two kidney-one clip (2K-1C), one kidney-one clip (1K-1C), deoxycorticosterone-salt (DOCA), and N-omega-nitro-L-arginine-methyl ester (L-NAME) groups. Mean arterial blood pressures were significantly higher in four hypertensive groups compared with control and sham groups. The active avoidance training results indicated that hypertension state is associated with learning impairment. Thiobarbituric acid-reactive substances (TBARS) were determined as an indicator of lipid peroxidation in brain and hippocampus. Additionally, brain and hippocampus nitrite levels were studied.