Age-related changes in apoptosis in rat hippocampus induced by oxidative stress.

Also known as programmed cell death, apoptosis is a sequence of events that leads to elimination of cells without releasing harmful substances into the surrounding area. Apoptosis may be induced by intracellular or extracellular signals. Certain apoptotic signals activate mitochondrial pro-apoptotic events and increase reactive oxygen species (ROS). Increased ROS production may lead to oxidative stress. The goal of our study was to characterize age-related changes in apoptosis induced by oxidative stress in the hippocampus. Rats 2, 7, 21 and 38 days old, and adult rats were used for our study. Hippocampal CA1, CA2, CA3 and dentate gyrus apoptosis, and hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels were measured. We found that numbers of hippocampal neurons were low in rats 2, 7 and 21 days old (CA1, p < 0.001; CA3, p < 0.05; gyrus dentatus, p < 0.001). The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cell count was highest in the CA1 and dentate gyrus of 21-day-old rats. Among 21-day-old rats, the hippocampal TBARS levels and SOD enzyme activity were high, whereas GPx activity was low. These results demonstrate that the hippocampal CA1 and dentate gyrus of 21-day-old rats are more prone to damage by oxidative stress.

Effect of melatonin on brain oxidative damage induced by traumatic brain injury in immature rats.

Progressive compromise of antioxidant defenses and free radical-mediated lipid peroxidation, which is one of the major mechanisms of secondary traumatic brain injury (TBI), has also been reported in pediatric head trauma. In the present study, we aimed to demonstrate the effect of melatonin, which is a potent free radical scavenger, on brain oxidative damage in 7-day-old rat pups subjected to contusion injury. Whereas TBI significantly increased thiobarbituric acid reactive substances (TBARS) levels, there was no compensatory increase in the antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) 24 hours after TBI in 7-day-old rats. Melatonin administered as a single dose of 5 mg/kg prevented the increase in TBARS levels in both non-traumatized and traumatized brain hemispheres. In conclusion, melatonin protects against oxidative damage induced by TBI in the immature brain.

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats.

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.

Effects of acute footshock stress on antioxidant enzyme activities in the adolescent rat brain.

In a previous study we demonstrated that acute footshock stress increased glutathione peroxidase activity in the prefrontal cortex and striatum of adult male rats. Adolescents may respond differently to stress as life stressors may be greater than at other ages. The present study examined the effects of the acute footshock stress on superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels in adolescent male and female rat brains. We demonstrated that acute footshock stress increased SOD activity in the prefrontal cortex, and increased GPx activity in the hippocampus in female rats. In males, acute footshock stress increased GPx activity in the prefrontal cortex and hippocampus. Footshock stress did not change TBARS levels. These results indicate a strong role of gender in the response of adolescent subjects to various aspects of stress.

Methamphetamine causes depletion of glutathione and an increase in oxidized glutathione in the rat striatum and prefrontal cortex.

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. The hypothesis that methamphetamine-induced neurotoxicity is mediated by reactive oxygen species was evaluated. It was found that acute administration of methamphetamine (5 and 15 mg kg(-1)) resulted in production of oxidative stress as demonstrated by decreased glutathione and increased oxidized glutathione levels in the rat striatum and prefrontal cortex. These changes in glutathione and oxidized glutathione levels were dose-dependent in striatum but not in prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

Antioxidant enzyme levels in intestinal and renal tissues after a 60-minute exercise in untrained mice.

The present study was designed to determine the effects of exercise on the antioxidant enzymatic system and lipid peroxidation in small intestine and kidney, during the post-exercise period in untrained mice. Two days after the last adaptation running exercise, animals were ran on the treadmill for 60 min at 18 m/min. 5 degrees slope. After the acute exercise the animals were killed by cervical dislocation, immediately (0 h), 3 hours (3 h) and 24 hours (24 h) after the exercise. Control animals were killed without running exercise. Their proximal small intestinal and renal tissues were quickly removed. Changes in the concentration of thiobarbituric acid reactive substance (TBARS), as an index of lipid peroxidation, in intestine and kidney were studied in mice after the running exercise and in unexercised control group. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined in these tissues. Tissue SOD, GPx activities and TBARS level were not increase by the exercise in kidney. Intestinal SOD activity decreased after exercise (0 h and 3 h respectively, p<0.05, p<0.01) and retumed to control levels. Intestinal GPx activity increased after exercise (0 h, p<0.05) and returned to control levels. There was no significant difference among groups in intestinal tissue TBARS levels. These findings could suggest that submaximal exercise may not cause oxidative stress in proximal small intestinal tissue and kidney.

The effects of single dose of methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex.

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. In the present study, we demonstrated that a single dose (15 mg/kg) of methamphetamine results in production of oxidative stress as demonstrated by increased thiobarbituric acid reactive substances levels in the rat striatum and prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

The effect of moderate swimming exercise on antioxidant enzymes and lipid peroxidation levels in children.

Strenuous exercise is characterized by increased oxygen consumption and the disturbance between intracellular pro-oxidant and antioxidant homeostasis. Although there are several studies related to an increase in antioxidant enzyme activity in adults doing exercise, the effect of regular exercise on antioxidant enzymes and lipid peroxidation levels has not been examined in children. In our study, the effects of a four week regular swimming exercise on antioxidant enzymes (superoxide dismutase and glutathione peroxidase) activities in erythrocytes and plasma thiobarbituric acid reactive substances (TBARS) levels, an indicator of lipid peroxidation, were investigated in previously untrained healthy children. We found that superoxide dismutase (SOD) activity was increased significantly following a four week swimming course (from 581.1 +/- 146.2 to 791.1 +/- 221.9 U/gHb, P < 0.01). Conversly, plasma TBARS levels were decreased from 1.1 +/- 0.4 to 0.9 +/- 0.3 nmol/ml (P < 0.05). Glutathione peroxidase (GPx) activity appeared to increase following swimming course, albeit not statistically significant (from 45.5 +/- 16.5 to 50.3 +/- 14.8 U/gHb). According to these findings, regular swimming exercise has beneficial effects on antioxidant defence in healthy children.

Effects of footshock stress on superoxide dismutase and glutathione peroxidase enzyme activities and thiobarbituric acid reactive substances levels in the rat prefrontal cortex and striatum.

Mild footshock stress results in an increase dopamine metabolism in the prefrontal cortex. Increases in either the intensity or duration of stress enhance dopamine metabolism in the nucleus accumbens and striatum, as well as in the prefrontal cortex. Dopamine is metabolized by monoamine oxidase with hydrogen peroxide as a product. In this study we have demonstrated that while very mild (0.2 mA) footshock stress did not change glutathione peroxidase activity in the rat prefrontal cortex and striatum, more intense (1.6 mA) footshock stress increased glutathione peroxidase activity at 0, 15, 30 and 60 min after the footshock in the prefrontal cortex and at 30 min after the footshock in the striatum. Stress did not change superoxide dismutase activity and thiobarbituric acid reactive substances levels. These results indicate that increased dopamine metabolism induced by footshock stress is probably responsible for the increase of glutathione peroxidase activity.

Lipid peroxidation and antioxidant enzyme levels of intestinal renal and muscle tissues after a 60 minutes exercise in trained mice.

To investigate the effect of blood perfusion difference on oxidant status, mice were trained by a 7-week running program. Two days after the last training session, mice were exercised for 60 minutes at the same training intensity. Changes in the concentration of thiobarbituric acid reactive substance (TBARS), as an index of lipid peroxidation, in intestine, kidney and muscle, were studied in trained mice immediately (0 h), 3 h and 24 h after the running exercise and in unexercised control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and xanthine oxidase (XO) were determined in these tissues. Tissue SOD activities were unaffected by the exercise. Muscle GPx activity increased after exercise (0 h and 3 h group, P < 0.01) and returned to control levels at 24 h, but there was not any significant difference in intestinal and renal tissues. Renal tissue XO activity could not be determined. There was not any significant difference among groups in intestinal tissue XO activity. The activity of XO was decreased only in skeletal muscle at 0 h (P < 0.05). TBARS levels of exercised groups were higher than control in muscle (P < 0.01). Intestinal TBARS levels decreased at 0 h (P < 0.05), than reached to control level. Renal TBARS levels of 0 h and 24 h group was higher than control (P < 0.01, P < 0.01 respectively). The results show that a long distance running exercise may cause lipid peroxidation damage in skeletal muscle and kidney.

Aerobic and anaerobic training effects on the antioxidant enzymes of the blood.

The purpose of the present study was to investigate the effects of aerobic and anaerobic training on serum lipid peroxidation levels and on antioxidant enzyme activities. Long distance runners for aerobic training group, and wrestlers for anaerobic training group were chosen. Non-sporting men were used as control group. When the aerobic power was compared; indirect VO2max of long-distance runners were found higher than wrestlers and control group (p<0.001, p<0.001). When lipid peroxidation levels were compared; levels of the thiobarbituric acid reactive substances (TBARS) of long distance runners were found to be lower than those in the control group (p<0.05), but similar to those found in wrestlers. Comparison of antioxidant enzyme activities in erythrocytes show that there were no significant difference among the groups in superoxide dismutase enzyme activities, but glutathione peroxidase (GPx) activity of long distance runners was higher than that measured in wrestlers (p<0.05). These results suggest that aerobic training increased in erythrocytes GPx activity with a subsequent decrease in plasma TBARS levels but anaerobic training had no effect on this process.

Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum.

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.

Lipid peroxidation and antioxidant activity in chronic haemodialysis patients treated with recombinant human erythropoietin.

In anaemia of chronic renal failure, the most important factor in the shortened erythrocyte survival may be lipid peroxidation of the cell membrane. Defective antioxidant activity may increase this damage. Although recombinant human erythropoietin (r-HuEPO) can effectively correct anaemia in chronic haemodialysis patients, its actions on lipid peroxidation and antioxidant activity are not clear. These actions were investigated in 13 patients undergoing chronic haemodialysis. Antioxidant activity, including red blood cell superoxide dismutase and total glutathione peroxidase levels and the lipid peroxidation product malondialdehyde, were measured before and 3 months after initiation of r-HuEPO treatment, using heparinized venous whole blood for cell and plasma determinations. Age-matched healthy volunteers were controls. Significantly higher levels of superoxide dismutase and total glutathione peroxidase were found in the patients than in the controls (p < 0.01). Plasma malondialdehyde levels were not affected by r-HuEPO. The results are explained by erythropoiesis and cellular haemoglobin synthesis due to r-HuEPO, followed by increase of circulating young red cells. The membranes of these young cells contain more antioxidant enzymes than the others. Despite r-HuEPO treatment, plasma malondialdehyde levels in haemodialysis patients may be higher than normal because of the uraemic milieu and the chronic haemodialysis.