The effects of oxytocin on cognitive defect caused by chronic restraint stress applied to adolescent rats and on hippocampal VEGF and BDNF levels.

BACKGROUND: Because brain development continues during adolescence, the effects of chronic stress on hippocampal changes that occur during that period are permanent. Oxytocin, which is synthesized in the hypothalamus and has many receptors in brain regions, including the hippocampus, may affect learning-memory. This study aimed to investigate chronic restraint stress on hippocampal functions, and hippocampal vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in adolescent male and female rats and the role of oxytocin in these effects. MATERIAL/METHODS: Experimental groups included control, stress+oxytocin, and stress+saline groups. Restraint stress was applied to all the stress groups for 1 h/day, for 7 days. Learning-memory tests were performed after the 7th day. RESULTS: In the stress+oxytocin groups, the process of finding the platform was shorter than in others groups. The stress+saline groups spent less time, whereas the stress+oxytocin groups spent more time, on the target quadrant in the probe trial. In the stress+oxytocin groups thigmotaxis time (indicating anxiety) decreased, but VEGF and BDNF levels increased. A positive correlation was found between VEGF and BDNF levels and the time spent within the target quadrant. CONCLUSIONS: The results indicate that impaired hippocampal learning and memory loss due to chronic restraint stress can be positively affected by intranasal oxytocin.

Preliminary investigation of sensitive biomarkers of trace metal pollution in mussel (Mytilus galloprovincialis) from Izmir Bay (Turkey).

The aim of this study was to identify possible relationships between biochemical- superoxide dismutase (SOD), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS) of mussels (Mytilus galloprovincialis) and chemical (Hg, Cd, Pb, Cr, Cu, Zn, Mn and Fe) contaminants from relatively clean area (Middle Bay) and heavily polluted area (Inner Bay) of the Izmir Bay. Sampling of mussels was performed in the beginning of May 2004. Mussel digestive glands have been used for biochemical assays. Trace metal content was determined by atomic absorption spectrophotometer using standard procedures. Metal contents in mussels collected at polluted site increased compared to the middle part of the bay. While there was a positive correlation between metals and SOD enzyme activity, there was a negative correlation between metals and GPx enzyme activity. An increase was observed in SOD enzyme activity and a decrease of GPx enzyme activity at the inner part of the bay.

The effect of melatonin on endotoxemia-induced intestinal apoptosis and oxidative stress in infant rats.

OBJECTIVE: To evaluate the effect of melatonin on the intestinal apoptosis along with oxidative damage in endotoxemic infant rats. DESIGN AND SETTING: Prospective animal study in a university-based experimental research laboratory. SUBJECTS AND INTERVENTIONS: Wistar albino 7-day-old rat pups (n=21). The animals were randomized into three experimental groups: (1) controls; (2) endotoxemia; (3) endotoxemia treated with melatonin (10mg/kg). Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (Escherichia coli serotype 0111:B4; 3 mg/kg). MEASUREMENTS AND RESULTS: Four hours after LPS injection, the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and thiobarbituric acid reactive substance (TBARS) levels as an indicator of lipid peroxidation, were determined. Intestinal apoptosis was assessed by hematoxylin-eosin staining and terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling. The administration of melatonin into endotoxemic rats prevented the increase in the TBARS levels, and increased the activities of antioxidant enzymes and attenuated apoptotic cell death in both intestinal epithelium and lamina propria. CONCLUSIONS: Melatonin diminished the intestinal oxidative stress and apoptotic damage induced by endotoxemia in infant rats.

Does antioxidant supplementation alter the effects of acute exercise on erythrocyte aggregation, deformability and endothelium adhesion in untrained rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.

Protective effects of erythropoietin against ethanol-induced apoptotic neurodegenaration and oxidative stress in the developing C57BL/6 mouse brain.

The developing central nervous system is extremely sensitive to ethanol, with well-defined temporal periods of vulnerability. Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain. Furthermore, acute ethanol administration produces lipid peroxidation in the brain as an indicator of oxidative stress. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection, and repair of the nervous system. In the present study, we investigated the effect of EPO against ethanol-induced neurodegeneration and oxidative stress in the developing C57BL/6 mouse brain. Seven-day-old C57BL/6 mice were divided into three groups: control group, saline-treated group, EPO-treated group. Ethanol was administered to mice at a dosage of 2.5 g/kg for two times with a 2-h interval. Recombinant human EPO (rhEPO) was given 1000 U/kg. Twenty-four hours after the first dose of ethanol, all the animals were killed. Neuronal cell death, apoptosis, thiobarbituric acid substance (TBARS) levels, superoxide dismutase (SOD), and glutathione peroxidase (Gpx) enzymes activities were evaluated. Histopathological evaluation demonstrated that EPO significantly diminished apoptosis in the cerebellum, prefrontal cortex, and hippocampus and also spared hippocampal CA1, CA2, and CA3 neurons. Simultaneous administration of EPO along with ethanol attenuated the lipid peroxidation process and restored the levels of antioxidants. Regarding the wide use of erythropoietin in premature newborns, this agent may be potentially beneficial in treating ethanol-induced brain injury in the perinatal period.

Effect of L-carnitine on diabetogenic action of streptozotocin in rats.

OBJECTIVES: L-carnitine is a naturally compound widely distributed in the body. It has an antiradical effect and decreases lipid peroxidation. In acute or chronic streptozotocin (STZ)-induced diabetic rats, the pancreatic content of carnitine was found to be significantly lower than nondiabetic group. We investigated the effects of L-carnitine on the development of STZ-induced diabetes in rats, to determine if L-carnitine can prevent the onset of diabetes or reduce the severity of hyperglycemia and this prevention/reduction is associated with the reduction in oxidative stress. SETTING AND DESIGN: The rats were divided into 3 groups: Control, STZ-treated (65 mg/kg intraperitoneally) and L-carnitine (500 mg/kg) and STZ-treated. METHODS: Oxidative stress was assessed by measuring pancreatic thiobarbituric acid reactive substance (TBARS) formation levels using the method of Rehncrona et al, pancreatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities using a Randox test combination (RANSOD and RANDOX). RESULTS: L-carnitine did not prevent the onset of diabetes at this dose. Development of diabetes was associated with an increase in pancreatic TBARS (0.028 +/- 0.008 and 0.046 +/- 0.017 nmol/mg Protein, respectively), and GPx activity (0.067 +/- 0.011 and 0.098 +/- 0.016 U/mg Protein, respectively). MAIN FINDINGS: L-carnitine prevented this increase induced by diabetes; TBARS (0.039 +/- 0.006 nmol/mg Protein) and GPx activity (0.053 +/- 0.011 U/mg Protein). CONCLUSION: These results suggest that L-carnitine exerts anti-oxidative effect in experimental diabetes.

Age-dependent effects of maternal deprivation on oxidative stress in infant rat brain.

Developing brain is much more sensitive to all kind of stressors than the developed brain. Early maternal deprivation causes some behavioural and physiological effects on rats. After the birth, there is no endocrinological response to stressors between post-natal 4 and 14th days, which is called stress-hyporesponsive period (SHRP) in rats. This hypo-responsiveness is time- and stressor-specific, as some more severe stressors have been shown to induce a stress response. The present study examined the effects of maternal deprivation on oxidative stress in the hippocampus, prefrontal cortex (PFC) and striatum regions of the brain both during and after SHRP of the infant rats. The results showed that maternal deprivation in SHRP increased antioxidant enzyme activities and reduced lipid peroxidation in infant rat brain. However, by the termination of SHRP, maternal deprivation reduced enzyme activities and increased lipid peroxidation. The results indicated that infant brain might be protected in SHRP from maternal deprivation-induced oxidative stress.

The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory.

It is known that positive effects of regular aerobic exercise on cognitive functions in humans and also animals; but how to the effects of aerobic exercise in adolescent period is unknown. The present study examined the effects of regular aerobic exercise on spatial memory using the Morris water maze, cell density and apoptosis of hippocampus in adolescent rats. Twenty-two days of age male rats were run on a treadmill for 30 min/session at a speed of 8m/min and 0 degrees slope, five times a week for 8 weeks. The present study showed that exercise induced significant cognitive improvement throughout brain maturation in rats. The number of hippocampal CA1 and CA3 neurons, and gyrus dentatus neurons were significantly increased in the exercised rats. There was no significant difference of CA2 neuron density between exercise and control groups. There was no significantly differences in any groups according to the results of apoptosis that account of TUNEL positive cells. The present results suggest that regular moderate aerobic treadmill exercise benefit in cognitive functions. This result may derive from treadmill exercise-induced increase cell density without altering of apoptosis in the hippocampus and dentate gyrus of adolescent rats.

Erythropoietin increases glutathione peroxidase enzyme activity and decreases lipid peroxidation levels in hypoxic-ischemic brain injury in neonatal rats.

BACKGROUND: We have previously shown that erythropoietin (Epo) exerts neuroprotective effects in the Rice-Vannucci model of neonatal hypoxic-ischemic brain injury. However, the mechanisms of Epo protection in this model are still unclear. OBJECTIVES: In the present study, we studied the effects of systemically administered Epo on lipid peroxidation levels and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities following hypoxic-ischemic brain injury in neonatal rats. METHODS: Seven-day-old Wistar rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. Brain lipid peroxidation levels and antioxidant enzyme activities were measured in the injured hemispheres 24 h after the hypoxic-ischemic insult. RESULTS: Hypoxic-ischemic injury significantly increased the thiobarbituric acid-reactive substance levels in the injured hemispheres as compared to the control group. In addition, glutathione peroxidase activity was significantly elevated in Epo-treated animals compared to saline-treated animals and the control group. CONCLUSIONS: These results suggest that Epo exerts neuroprotective effects against hypoxic-ischemic brain injury at least partially via the modulation of antioxidant enzyme activity.

Positive effects of deprenyl and estradiol on spatial memory and oxidant stress in aged female rat brains.

Increasing age decreases spatial learning and memory. Spatial learning is coordinated with different brain regions. Since the oxidative damage may play a role in the aging process, including the associated cognitive decline, age-related impairment in spatial learning and memory may be alleviated by antioxidant treatment. The present study examined the effects of the monoamine oxidase B inhibitor L-deprenyl, alone and in combination with estradiol, on spatial memory using the Morris water maze and oxidant stress in aged female rat brains. We demonstrated that co-administration of deprenyl and estradiol caused a synergistic effect on spatial memory. However, use of either deprenyl or estradiol alone increased antioxidant enzyme activities in brain and reduced lipid peroxidation. Therefore, positive effects of deprenyl and estradiol on spatial memory may occur due not only to their antioxidant activities but also to the different actions.

Effects of sprint exercise on oxidative stress in skeletal muscle and liver.

Although numerous studies have tested the effects of continuous exercise regimens on antioxidant defences, information on the effect of sprint exercise on the antioxidant defence system and lipid peroxidation levels of tissues is scant. The present study was designed to determine the effects of sprint exercise on the lipid peroxidation and antioxidant enzyme system in liver and skeletal muscle during the post-exercise recovery period in untrained mice. Mice performed 15 bouts of exercise, each comprising running on a treadmill for 30 s at 35 m.min(-1) and a 5 degrees slope, with a 10-s rest interval between bouts. They were then killed by cervical dislocation either immediately (0 h), 0.5 h, 3 h or 24 h after completion of the exercise. Their gastrocnemius muscle and liver tissues were quickly removed. It was found that blood lactate levels increased immediately after the exercise, but had returned to control levels by 0.5 h post-exercise. This exercise regimen had no effect on the activity of superoxide dismutase and glutathione peroxidase in these tissues. Levels of muscle thiobarbituric acid reactive substances (TBARS) had increased at 0.5 and 3 h post-exercise, and then returned to control levels by 24 h post-exercise. In conclusion, acute sprint exercise in mice resulted in an increase in TBARS levels in skeletal muscle; no change was observed in the liver. Antioxidant enzyme activities remained unaffected by acute sprint exercise in these tissues.