Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system

This study investigated the onset of age-related changes in the myocardial antioxidant defense system (ADS) and the vulnerability of the myocardium to oxidative stress following exercise training. Few studies have investigated the influence of the most prevalent life-prolonging strategy physical exercise, on the age-dependent alterations in the myocardial antioxidant enzyme system of female rats at mid age and to determine whether exercise-induced ADS could attenuate lipid peroxidation. Two age groups young (3 months old) and mid age (12 months old) Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. We found a striking decrease (p < 0.01) in the activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the myocardium of mid aged rats when compared to young rats by 36, 50 and 29%, respectively, suggesting the onset of age-dependent decrease in the myocardial ADS. A similar age-related decrease (p < 0.01) was observed in the reduced glutathione (GSH) content (36%). Despite the reduction in ADS, lipid peroxidation (LPO) (20%) was also decreased. In contrast, exercise training significantly elevated (p < 0.01) these antioxidant enzyme activities and the content of GSH. The increase in SOD and CAT activities were more pronounced in the mid aged rats when compared to younger rats, but increased the level of lipid peroxidation to higher levels in the mid-age group following the training regimen. The findings of the present study suggest that, although the activity levels of the myocardial antioxidant enzymes were elevated with the 12 weeks of exercise training, the changes were not sufficient enough in attenuating oxidative stress in the myocardium of female rats during this short period of exercise training.     

Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: Influence of exercise training on antioxidant defense system

This study investigated the onset of age-related changes in the myocardial antioxidant defense system (ADS) and the vulnerability of the myocardium to oxidative stress following exercise training. Few studies have investigated the influence of the most prevalent life-prolonging strategy physical exercise, on the age-dependent alterations in the myocardial antioxidant enzyme system of female rats at mid age and to determine whether exercise-induced ADS could attenuate lipid peroxidation. Two age groups young (3 months old) and mid age (12 months old) Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. We found a striking decrease (p < 0.01) in the activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the myocardium of mid aged rats when compared to young rats by 36, 50 and 29%, respectively, suggesting the onset of age-dependent decrease in the myocardial ADS. A similar age-related decrease (p < 0.01) was observed in the reduced glutathione (GSH) content (36%). Despite the reduction in ADS, lipid peroxidation (LPO) (20%) was also decreased. In contrast, exercise training significantly elevated (p < 0.01) these antioxidant enzyme activities and the content of GSH. The increase in SOD and CAT activities were more pronounced in the mid aged rats when compared to younger rats, but increased the level of lipid peroxidation to higher levels in the mid-age group following the training regimen. The findings of the present study suggest that, although the activity levels of the myocardial antioxidant enzymes were elevated with the 12 weeks of exercise training, the changes were not sufficient enough in attenuating oxidative stress in the myocardium of female rats during this short period of exercise training.     

Response of hepatic antioxidant system to exercise training in aging female rat

This study was undertaken to investigate the effect of exercise training on aging in the hepatic oxidative status and antioxidant defense of female albino rat. Two age groups of 3 months and 12 months old Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. The antioxidant enzyme assays were carried out by the standard methods. Lower (P<0.01) activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) by 21%, 44% and 63% respectively was observed in the older rats when compared to younger rats. Also, glutathione (GSH) levels were 42% lower (P<0.01) in older than younger animals. Exercise training to the 12 months aged rats significantly (P<0.01) elevated these antioxidant enzyme activities and GSH content, when compared to older control rats. These levels are almost equal to the values observed in the younger control rats. The levels of lipid peroxidation end product, malondialdehyde (MDA) the major indicator of oxidative stress, was found to increase with age (11%) and exercise training caused further elevation (28% of control). The present findings imply that the reactive oxygen species that are generated due to aging process were detoxified by the exercise induced antioxidant system in the liver tissue. These findings are also in agreement with similar changes in male animals, which clearly envisage no gender difference in the amelioration of the antioxidant enzyme system in older age due to exercise. In conclusion, it can be stated that twelve weeks treadmill exercise training has beneficial effect in improving antioxidant defense capacity by augmenting SOD, CAT and GR activities and GSH levels of older rats, thereby preventing oxidative damage to the liver tissue.     

Exercise training with ageing protects against ethanol induced myocardial glutathione homeostasis

Glutathione plays a central role in the maintenance of cellular antioxidant defense. The alterations in the glutathione and associated recyclic enzymes caused by both exercise training and ethanol are well documented; however, their interactive effects with age are not well understood. Therefore, the influence of ageing and the interactive effects of exercise training and ethanol on the myocardial glutathione system in 3 months and 18 months old rats were examined. The results showed a significant (p<0.01) reduction in GSH content, Se and non-Se GSH-Px, GR and GST activities in the myocardium of rat with age. A significant increase (p<0.05) in the activities of these enzymes was observed in both age groups of rats in response to exercise training. This exercise-induced elevation of Se and non-Se GSH-Px and GR activities was more pronounced in the 18 months old rats when compared to 3 months old rats. Ethanol consumption significantly (p<0.05) reduced the GSH content, Se and non-Se GSH-Px and GR activities in both age groups of rats. In contrast, ethanol consumption significantly (p<0.05) increased the activity of GST. The combined action of exercise plus ethanol significantly (p<0.05) elevated the GSH content, Se and non-Se GSH-Px, GR and GST activities when compared to the ethanol treated rats in both age groups, indicating the suppression of ethanol-induced oxidative stress by exercise training. In conclusion, there was a compensatory myocardial response lessening ethanol-induced oxidative stress by exercise training, which seemed to result from the higher activity of glutathione recycling and utilizing enzymes, which may be critical for preventing chronic oxidative damage to the myocardium during ageing and even due to ethanol consumption.     

Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.     

Exercise training with ageing protects against ethanol induced myocardial glutathione homeostasis

Glutathione plays a central role in the maintenance of cellular antioxidant defense. The alterations in the glutathione and associated recyclic enzymes caused by both exercise training and ethanol are well documented; however, their interactive effects with age are not well understood. Therefore, the influence of ageing and the interactive effects of exercise training and ethanol on the myocardial glutathione system in 3 months and 18 months old rats were examined. The results showed a significant (p<0.01) reduction in GSH content, Se and non-Se GSH-Px, GR and GST activities in the myocardium of rat with age. A significant increase (p<0.05) in the activities of these enzymes was observed in both age groups of rats in response to exercise training. This exercise-induced elevation of Se and non-Se GSH-Px and GR activities was more pronounced in the 18 months old rats when compared to 3 months old rats. Ethanol consumption significantly (p<0.05) reduced the GSH content, Se and non-Se GSH-Px and GR activities in both age groups of rats. In contrast, ethanol consumption significantly (p<0.05) increased the activity of GST. The combined action of exercise plus ethanol significantly (p<0.05) elevated the GSH content, Se and non-Se GSH-Px, GR and GST activities when compared to the ethanol treated rats in both age groups, indicating the suppression of ethanol-induced oxidative stress by exercise training. In conclusion, there was a compensatory myocardial response lessening ethanol-induced oxidative stress by exercise training, which seemed to result from the higher activity of glutathione recycling and utilizing enzymes, which may be critical for preventing chronic oxidative damage to the myocardium during ageing and even due to ethanol consumption.     

Effect of aerobic exercise intervention on DDT degradation and oxidative stress in rats

Dichlorodiphenyltrichloroethane (DDT) reportedly causes extensively acute or chronic effects to human health. Exercise can generate positive stress. We evaluated the effect of aerobic exercise on DDT degradation and oxidative stress.Main methods: Male Wistar rats were randomly assigned into control (C), DDT without exercise training (D), and DDT plus exercise training (DE) groups. The rats were treated as follows: DDT exposure to D and DE groups at the first 2 weeks; aerobic exercise treatment only to the DE group from the 1st day until the rats are killed. DDT levels in excrements, muscle, liver, serum, and hearts were analyzed. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Aerobic exercise accelerated the degradation of DDT primarily to DDE due to better oxygen availability and aerobic condition and promoted the degradation of DDT. Cumulative oxidative damage of DDT and exercise led to significant decrease of SOD level. Exercise resulted in consistent increase in SOD activity. Aerobic exercise enhanced activities of CAT and GSH-Px and promoted MDA scavenging. Results suggested that exercise can accelerate adaptive responses to oxidative stress and activate antioxidant enzymes activities. Exercise can also facilitate the reduction of DDT-induced oxidative damage and promoted DDT degradation. This study strongly implicated the positive effect of exercise training on DDT-induced liver oxidative stress.     

The effects of oxidative stress in urinary tract infection during pregnancy

The purpose of this study was to determine the effect of urinary tract infection (UTI) on antioxidant systems and lipid peroxidation (LPO) levels during pregnancy. We also investigated if these antioxidant systems and LPO levels differed in each trimester. One hundred forty-three nonpregnant women, as a control group, and 77 pregnant women were included in the study. Urine cultures were performed according to standard techniques. Catalase (CAT), superoxide dismutase (SOD), and LPO levels were measured using a spectrophotometer. UTI was observed in 14 of 77 pregnant women and the isolated microorganisms were Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus. CAT, SOD, and LPO levels were increased in pregnant women compared with nonpregnant women (P<.01). CAT, SOD activities, and LPO levels were increased from the first trimester to the third trimester in pregnancy without UTI. However, CAT and SOD activities were decreased, LPO levels were increased from the first trimester to the third trimester in pregnancy with UTI (P<.01). Pregnancy causes oxidative stress and also UTI during pregnancy may aggravate oxidative stress.     

The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats

The effect of exercise on oxidant stress and on alterations in antioxidant defense in elderly has been investigated extensively. However, the impact of regularly performed long-term physical activity starting from adulthood and prolonged up to the old age is not yet clear. We have investigated the changes in the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) - and lipid peroxidation in various tissues of rats which had performed (old-trained) or had not performed (old-control) regular swimming exercise for one year. These animals were compared with young-sedentary rats. Increased lipid peroxidation was observed with ageing in all tissues (heart, liver, kidney, striated muscle) and swimming had no additional effect on this elevation of lipid peroxidation. Heart and striated muscle SOD activites, and striated muscle CAT activity increased as a consequence of ageing, whereas kidney and liver CAT activities, as well as GPx activities in kidney, liver, lung and heart were significantly decreased compared to young controls. Lung and heart SOD, liver CAT activities as well as GPx activities in liver, lung and heart were increased significantly in rats which performed exercise during ageing, compared to the old-control group. These findings suggest that lifelong exercise can improve the antioxidant defense in many tissues without constituting any additional oxidant stress.     

Oxidative damage following cerebral ischemia depends on reperfusion - a biochemical study in rat

The extent of brain injury during reperfusion appears to depend on the experimental pattern of ischemia/reperfusion. The goals of this study were: first, to identify the rate of free radicals generation and the antioxidant activity during ischemia and reperfusion by means of biochemical measurement of lipid peroxidation (LPO) and both enzymatic (superoxid dismutase - SOD, catalase - CAT, glutathion peroxidase - GPx) and non-enzymatic antioxidants activity (glutathione - GSH); and second, to try to find out how the pattern of reperfusion may influence the balance between free radical production and clearance. Wistar male rats were subject of four-vessel occlusion model (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two atraumatic arterial microclamps placed on carotid arteries. The level of free radicals and the antioxidant activity were measured in ischemic rat brain tissue homogenate using spectrophotometrical techniques. All groups subjected to ischemia shown an increase of LPO and a reduction of the activity of enzymatic antioxidative systems (CAT, GPx, SOD) and non-enzymatic systems (GSH). For both groups subjected to ischemia and reperfusion, results shown an important increase of LPO but less significant than the levels found in the group with ischemia only. Statistically relevant differences (p<0.01) between continuous reperfusion and fragmented reperfusion were observed concerning the LPO, CAT, SOD and GSH levels, oxidative aggresion during fragmented reperfusion being more important.     

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid.

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.     

Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats

Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The results indicate NDEA-induced oxidative stress and alteration in antioxidant enzymes in liver and kidney to neutralise oxidative stress.     

Vascular redox imbalance in rats submitted to chronic exercise

Exercise training has been used for treatment/prevention of many cardiovascular diseases, but the mechanisms need to be clarified. Thus, our aim was to compare oxidative stress parameters between rats submitted to a swimming training and sedentary rats (control). Twelve male rats were divided into two groups: control and exercise training. The exercise training had daily 1 h swimming sessions for 8 weeks and a load (5% of its body mass) was placed in rat's tail. Thereafter the animals were killed, aorta and heart were surgically removed and blood was collected. Body mass gain, thiobarbituric acid reactive species (TBARS), carbonyl content, total reactive antioxidant potential (TRAP), total antioxidant reactivity (TAR), superoxide dismutase (SOD) activity and catalase (CAT) activity were evaluted. The trained rats showed a lower body mass gain and no modifications on heart. An increased SOD activity was observed on aorta after the training, but no changes were seen for CAT activity, which led to an increased SOD/CAT ratio. The arterial TBARS was also increased for trained rats. The decrease in TRAP in exercise training was the single modification on plasma. Our findings suggest that the increased SOD activity could play a role in vascular adaptations to exercise training. Copyright © 2010 John Wiley & Sons, Ltd.     

The influence of season on oxidant-antioxidant status in trained and sedentary subjects

The association between oxidative stress and cardiovascular diseases is a widely accepted fact today. Generally, men have a higher risk of cardiovascular incidents and mortality from acute myocardial infarction and strokes. We have examined sport-associated circannual rhythms of oxidant and antioxidant processes by measuring plasma LPO, erythrocyte SOD, CAT, Gpx activity and plasma hormonal status in both sedentary and long-term trained men and women. We have shown seasonal variations in both oxidant and antioxidant status in all examined groups. The largest difference was observed in the oxidant status between sedentary men and women during autumn and winter, which is considered a period of high coronary risk for men. Sport decreased LPO in trained men in autumn, while the same effect in trained women was shifted towards summer. These data state that regular, long-term physical exercise training induces adaptive responses that confer protection against oxidative stress, as well as the beneficial effect of exercise with regard to season, particularly in men during a period of high coronary risk (autumn and winter, respectively) and in women during summer.     

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer     

Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle

Several redox-regulated responses to an acute exercise bout fail in aged animal skeletal muscle, including the ability to upregulate the expression of antioxidant defense enzymes and heat shock proteins (HSPs). These findings are generally derived from studies on sedentary rodent models and thus may be related to reduced physical activity and/or intraspecies differences as opposed to aging per se. This study, therefore, aimed to determine the influence of age and training status on the expression of HSPs, antioxidant enzymes, and NO synthase isoenzymes in quiescent and exercised human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis before and 3 days after an acute high-intensity-interval exercise bout in young trained, young untrained, old trained, and old untrained subjects. Levels of HSP72, PRX5, and eNOS were significantly higher in quiescent muscle of older compared with younger subjects, irrespective of training status. 3-NT levels were elevated in muscles of the old untrained but not the old trained state, suggesting that lifelong training may reduce age-related macromolecule damage. SOD1, CAT, and HSP27 levels were not significantly different between groups. HSP27 content was upregulated in all groups studied postexercise. HSP72 content was upregulated to a greater extent in muscle of trained compared with untrained subjects postexercise, irrespective of age. In contrast to every other group, old untrained subjects failed to upregulate CAT postexercise. Aging was associated with a failure to upregulate SOD2 and a downregulation of PRX5 in muscle postexercise, irrespective of training status. In conclusion, lifelong training is unable to fully prevent the progression toward a more stressed muscular state as evidenced by increased HSP72, PRX5, and eNOS protein levels in quiescent muscle. Moreover, lifelong training preserves some (e.g., CAT) but not all (e.g., SOD2, HSP72, PRX5) of the adaptive redox-regulated responses after an acute exercise bout. Collectively, these data support many but not all of the findings from previous animal studies and suggest parallel aging effects in humans and mice at rest and after exercise that are not modulated by training status in human skeletal muscle.     

Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise

The association between physical exercise and oxidative damage in the skeletal musculature has been the focus of many studies in literature, but the balance between superoxide dismutase and catalase activities and its relation to oxidative damage is not well established. Thus, the aim of the present study was to investigate the association between regular treadmill physical exercise, oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen male Wistar rats (8-12 months) were randomly separated into two groups (trained n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in progressive exercise (velocity, time, and inclination). Training program consisted in a progressive exercise (10 m/min without inclination for 10 min/day). After 1 week the speed, time and inclination were gradually increased until 17 m/min at 10% for 50 min/day. After the training period animals were killed, and gastrocnemius and quadriceps were surgically removed to the determination of biochemical parameters. Lipid peroxidation, protein oxidative damage, catalase, superoxide dismutase and citrate synthase activities, and muscular glycogen content were measured in the isolated muscles. We demonstrated that there is a different modulation of CAT and SOD in skeletal muscle in trained rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were significantly decreased and, in contrast, a significant increase in protein carbonylation was observed. These results suggest a non-described adaptation of skeletal muscle against exercise-induced oxidative stress.     

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.     

Modulation of Antioxidant Enzyme Expression by PTU-Induced Hypothyroidism in Cerebral Cortex of Postnatal Rat Brain

This study aimed to elucidate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters and expression of antioxidant enzymes in cerebral cortex of rat brain during postnatal development. A significant decrease in levels of lipid peroxidation and H₂O₂ were seen in 7 and 30 days old PTU-treated rats with respect to their controls. Significantly decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old PTU-treated rats as compared to their respective controls. However, increase in translated product of CAT was seen in all age groups of PTU-treated rats. Glutathione peroxidase activity was decreased in 7 days and increased in 15 days old PTU-treated rats with respect to their control groups. Histological sections clearly show a decline in neuronal migration with neurons packed together in the hypothyroid group as compared to the control.     

Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid.

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.