Neuroprotective effects of zinc on antioxidant defense system in lithium treated rat brain

With a view to find out whether zinc affords protection against lithium toxicity the activities of antioxidant enzymes and lipid peroxidation profile were determined in the cerebrum and cerebellum of lithium treated female Sprague Dawley rats. Lipid peroxidation was significantly increased in both the cerebrum and the cerebellum of animals administered with lithium for a total duration of 4 months as compared to the normal control group. On the contrary, the activities of catalase and glutathione-s-transferase (GST) were significantly reduced after 4 months of lithium treatment. The activity of superoxide dismutase (SOD) was significantly increased in the cerebrum after 4 months lithium administration, whereas in the cerebellum the enzyme activity was unaffected. No significant change in the levels of reduced glutathione (GSH) was found in either cerebrum or cerebellum after 2 months of lithium treatment. However, 4 months lithium treatment did produce significant changes in GSH levels in the cerebrum and in the cerebellum. Zinc supplementation for 4 months in lithium-treated rats significantly increased the activities of catalase and GST in the cerebellum, showing that the treatment with zinc reversed the lithium induced depression in these enzyme activities. Though, zinc treatment tended to normalize the SOD activity in the cerebrum yet it was still significantly higher in comparison to normal levels. From the present study, it can be concluded that the antiperoxidative property of zinc is effective in reversing the oxidative stress induced by lithium toxicity in the rat brain.     

Physiological significance of catalase and glutathione peroxidases,and in vivo peroxidation,in selected tissues of the toadDiscoglossus pictus (Amphibia) during acclimation to normobaric hyperoxia

1. Various parameters related to oxidative stress were measured in adult Discoglossus pictus acclimated for 15 days to either normoxia or hyperoxia (PO2 = 710 mmHg). 2. Total weight of the toads and total and relative wet weight of liver, kidneys, lungs and heart were not changed by hyperoxic acclimation. 3. In vivo tissue peroxidation increased in lung, decreased in skeletal muscle, and was not changed in liver, kidney, heart and skin after hyperoxic exposure. 4. Hyperoxic acclimation increased catalase activities in the lung, liver, kidney and heart but not in skeletal muscle and skin. 5. Liver showed higher GSH-peroxidase activity with cumene-OOH than with H2O2 as substrate, whereas lung, skeletal muscle and skin presented similar GSH-peroxidase activities with both substrates. 6. GSH-peroxidase activities did not change between hyperoxic and normoxic animals in liver, lung, skeletal muscle and skin. 7. These results show that catalase, not GSH-peroxidase, is the principal H2O2 detoxifying enzyme involved in the adaptation of D. pictus to hyperoxia.     

Tellurium-induced dose-dependent impairment of antioxidant status: differential effects in cerebrum,cerebellum, and brainstem of mice

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-S-transferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.     

Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development

The protection of the developing organism from oxidative damage is ensured by antioxidant defense systems to cope with reactive oxygen species (ROS), which in turn can be influenced by dietary polyunsaturated fatty acids (PUFAs). PUFAs in membrane phospholipids are substrates for ROS-induced peroxidation reactions. We investigated the effects of dietary supplementation with omega-3 PUFAs on lipid peroxidation and antioxidant enzyme activities in rat cerebrum, liver and uterus. Pups born from dams fed a diet low in omega-3 PUFAs were fed at weaning a diet supplying low α-linolenic acid (ALA), adequate ALA or enriched with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Malondialdehyde (MDA), a biomarker of lipid peroxidation, and the activities of superoxide dismutase 1 (SOD1), SOD2, catalase (CAT) and glutathione peroxidase (GPX) were determined in the three target organs. Compared to low ALA feeding, supplementation with adequate ALA or with EPA + DHA did not affect the cerebrum MDA content but increased MDA content in liver. Uterine MDA was increased by the EPA + DHA diet. Supplementation with adequate ALA or EPA + DHA increased SOD2 activity in the liver and uterus, while only the DHA diet increased SOD2 activity in the cerebrum. SOD1, CAT and GPX activities were not altered by ALA or EPA + DHA supplementation. Our data suggest that increased SOD2 activity in organs of the growing female rats is a critical determinant in the tolerance to oxidative stress induced by feeding a diet supplemented with omega-3 PUFAs. This is may be a specific cellular antioxidant response to ROS production within the mitochondria.     

Alterations in Protective Enzymes Against Peroxidation in the Central and Peripheral Nervous System of Control and Dysmyelinating Mutant Mice

The activities of peroxide-detoxifying enzymes such as superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase were measured in the nervous system of neurological dysmyelinating mutants: quaking (Qk), shiverer (Shi), and trembler (Tr) mice. Cu/Zn-SOD activity was higher in the cerebellum of Qk and Shi mice (by 53% and 106%, respectively) in comparison with controls, but it was the same in the cerebellum of Tr mice and their corresponding controls. In contrast, there was no difference in the level of Cu/Zn-SOD activity in the cerebrum of Qk, Shi, and Tr mice and their respective controls. Mn-SOD activity was the same among all the mutants compared to control animals in both cerebrum and cerebellum. In Shi cerebellum, glutathione peroxidase and glutathione reductase activities were slightly decreased (a 21.6% and a 13.2% diminution, respectively), whereas catalase activity in cerebrum and cerebellum was the same among mutants and control mice. In the sciatic nerve from Tr mice, all the enzymatic activities were enhanced: sixfold increase for total SOD, and 2.4-fold, 3.5-fold, and 1.8-fold increase for glutathione peroxidase, glutathione reductase, and catalase, respectively.     

Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication

Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.     

Protective Role of Lithium in Ameliorating the Aluminium-induced Oxidative Stress and Histological Changes in Rat Brain

This study was carried out to investigate the effects of lithium (Li) supplementation on aluminium (Al) induced changes in antioxidant defence system and histoarchitecture of cerebrum and cerebellum in rats. Al was administered in the form of aluminium chloride (100 mg/kg b.wt./day, orally) and Li was given in the form of Li carbonate through diet (1.1 g/kg diet, daily) for a period of 2 months. Al treatment significantly enhanced the levels of lipid peroxidation and reactive oxygen species in both the cerebrum and cerebellum, which however were decreased following Li supplementation. The enzyme activities of catalase, superoxide dismutase (SOD) and glutathione reductase (GR) were significantly increased in both the regions following Al treatment. Li administration to Al-fed rats decreased the SOD, catalase and GR enzyme activities in both the regions; however, in cerebellum the enzyme activities were decreased in comparison to normal controls also. Further, the specific activity of glutathione-s-transferase and the levels of total and oxidized glutathione were significantly decreased in cerebrum and cerebellum following Al treatment, which however showed elevation upon Li supplementation. The levels of reduced glutathione were significantly decreased in cerebrum but increased in cerebellum following Al treatment, which however were normalized upon Li supplementation but in cerebellum only. Apart from the biochemical changes, disorganization in the layers of cerebrum and vacuolar spaces were also observed following Al treatment indicating the structural damage. Similarly, the loss of purkinje cells was also evident in cerebellum. Li supplementation resulted in an appreciable improvement in the histoarchitecture of both the regions. Therefore, the study shows that Li has a potential to exhibit neuroprotective role in conditions of Al-induced oxidative stress and be explored further to be treated as a promising drug against neurotoxicity.     

Oxidative stress correction by nicotinamide and nicotynol-GABA in diabetic neuropathy

Concentration of lipid peroxidation products and antioxidant enzyme activities in rat brain and erythrocytes and the effects of nicotinamide and nicotinoyl-GABA administration on these parameters were estimated on 21st day of streptozotocin-induced diabetes. It was demonstrated more then two-fold diabetes-induced accumulation of conjugated dienes and malondialdehyde in tissues studied. Superoxide dismutase and glutathione reductase activities of both brain homogenate and erythrocytes as well as catalase and glutathione peroxidase activities of brain homogenate were shown to decrease significantly in diabetic rats, meanwhile, catalase activity of erythrocytes was increased and glutathione peroxidase unchanged. So the correlation between changes in enzymatic antioxidant system in brain and erythocytes failed to be found. Alterations observed were virtually prevented by the course of nicotinamide and nicotinoyl-GABA treatment. The results suggested that the suppression of antioxidant system could be primary biochemical disturbance in diabetic neuropathy progression. It was shown that the antioxidant efficacy of nicotinoyl-GABA is lower than that of nicotinamide. It was suggested that the mechanism of antioxidant action of nicotinamide and its structural analogue consists of both scavenging of lipid peroxides and NAD biosynthesis that leads to activation and normalization of altered energy and lipid metabolism.     

Circadian rhythm disorders and dynamic changes of energy metabolism in rat heart muscle cells

The functional states of pro- and antioxidant systems in blood and heart muscle cells in rats with long-term emotional stress have been studied. It has been shown that daily rhythm disorders produce psycho-emotional stress in animals and that, this is accompanied by quantitative changes in physiological parameters and hormones in the blood. In the present study, it was observed that such stress increased lipid peroxidation in blood and heart muscle cells. Also, activities of antioxidant enzymes, superoxide dismutase, and catalase were diminished, indicating deterioration of the antioxidant system. In addition, there were decreased activities of mitochondrial enzymes participating in energy metabolism, indicating decreased energy levels in heart muscle cells. These results suggest the likelihood that emotional stress is a key factor that can cause a whole range of diseases of the cardiovascular system.     

Augmentation of antioxidant enzymes in vascular endothelium

The endothelium is a key site of injury from reactive oxygen species that can potentially be protected by the antioxidant enzymes superoxide dismutase and catalase. Large proteins, such as superoxide dismutase and catalase, do not readily penetrate cell membranes, which limits their efficacy in protecting cells from cellular reactions involving both intracellularly and extracellularly generated reactive oxygen species. Two methods are described that promote enzyme delivery to cultured endothelial cells and confer increased resistance to oxidative stress. The first method is to entrap the antioxidant enzymes within liposomes, which then become incorporated by endothelial cells and can increase enzyme specific activities by as much as 44-fold within 2 h. The second method involves covalent conjugation of polyethylene glycol (PEG) to superoxide dismutase and catalase, a technique that increases circulatory half-life and reduces protein immunogenicity. Conjugation of PEG to superoxide dismutase and catalase increased cellular-specific activities of these enzymes in cultured endothelial cells (but at a slower rate than for liposome entrapped enzymes) and rendered these cells more resistant to oxidative stress. Both liposome-mediated delivery and PEG conjugation offer an additional benefit over native superoxide dismutase and catalase because they can increase cellular antioxidant activities in a manner that can provide protection from both intracellular and extracellular superoxide and hydrogen peroxide.     

Age-related changes in the activity of antioxidant and redox enzymes in rats

Cellular defense system, including glutathione, glutathione-related enzymes, and antioxidant and redox enzymes, may play crucial roles in the aging of aerobic organisms. To understand the physiological roles of these factors in the aging process, their levels were compared in the livers and brains of 5-week- and 9-month-old rats. GST activity was higher in livers and brains of 9-month-old rats than in those of 5-week-old rats, and brain catalase activity was about 2-fold higher. However, it was unchanged in the livers of the 9-month-old rats. gamma-Glutamylcysteine synthetase activity was about 2-fold higher in the brains of the older rats but again not in their livers. In contrast glutathione synthetase activity appeared to be lower in the livers of the older rats while GSH content did not change with age in livers and brains. Glutathione peroxidase activity was higher in 9-month-old rat brains, but lower in 9-month-old rat livers, while superoxide dismutase activity was higher in both tissues in the older rats. The activities of two redox enzymes, thiol-transferase and thioredoxin reductase, did not change with age, nor did that of glutathione reductase. These results indicate that levels of different cellular defense systems vary with age in an irregular manner.     

Effect of vitamin E and selenium on antioxidant enzymes in brain,kidney and liver of cigarette smoke-exposed mice

The present study was conducted to evaluate the protective effects of vitamin E and selenium (Se) application on alteration of antioxidant enzyme activities against cigarette smoking induced oxidative damage in brains, kidneys and liver of mice. Male mice (balb/c) were exposed to cigarette smoke and treated with Se and/or vitamin E. Glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRX), superoxide dismutase (SOD) and catalase (CAT) enzyme activities in mice brain, kidney and liver were measured spectrophotometrically. GST, GPX, GRX, SOD and CAT enzyme activities in the brains of smoke-exposed mice were found lower than the enzymes activities of control mice and Se-and vitamin E-treated mice at the end of the three and five months. Opposite to brain, enzyme activities in kidneys and livers of smoke-exposed mice were found higher than the enzymes activities of control mice and Se-and vitamin E-treated mice at the end of the three and five months. Activities of GST, GPX, GRX SOD and CAT in the livers, kidneys and brains of smoke-exposed mice were found statistically different (p < 0.01) compared to control mice and Se-and vitamin E-treated mice. Combined application of vitamin E and Se had an additive protective effect against changing enzymes activities in smoke-exposed mice livers, kidneys and brains at the end of the both application periods. These results suggest that cigarette smoke exposure enhances the oxidative stress, thereby disturbing the tissue antioxidant defense system and combined application of vitamin E and Se protects the brain, kidney and liver from oxidative damage through their antioxidant potential.     

Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis.

The effect of experimental cryptorchidism on the level of oxidative stress and antioxidant functions in rat testis was studied. Adult male Sprague-Dawley rats were rendered unilaterally cryptorchid (by suturing one testis to the abdominal wall) and killed 1, 3, or 7 days after the operation. As an indicator of oxidative stress, lipid peroxidation was measured by the diene conjugation method in testis homogenates. The activities of the antioxidant enzymes were determined either in the 10,000 x g supernatant fraction (glutathione [GSH] peroxidase, GSH transferase, hexose monophosphate shunt) or in crude testis homogenates (superoxide dismutase, catalase). An expected reduction (48%) in weight of the abdominal testes was evident by postoperative Day 7. The catalytic activities per testis of superoxide dismutase (Cu/Zn form) and catalase were found to decrease in cryptorchidism. The effect was seen on the first postoperative day and was most profound on Day 7 after surgery. The principal antioxidant enzyme, superoxide dismutase, was most sensitive to cryptorchidism, the activity in the abdominal testes being 74% or 85% (per gram of tissue or per whole testis, respectively; p less than 0.01). After impairment of the reactive oxygen detoxifying capacity, lipid peroxidation was increased in the abdominal testis by 46% (p less than 0.01) on postoperative Day 7. Slight concomitant increases were detected in the activities of GSH-peroxidase (p less than 0.01), GSH-transferase (p less than 0.001), and the hexose monophosphate shunt (p less than 0.001). This effect was seen only when calculated per gram of tissue, not per whole testis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antioxidant levels in tissues of young and adult camels (Camelus dromedarius)

In this study, we measured the concentration of some antioxidant substances in erythrocytes hemolysate, liver, kidney and brain in young and adult camels. It has been found that the activity of the antioxidant enzymes glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and the concentration of glutathione, ascorbic acid and alpha-tocopherol are high in both young and adult camels. GSH-Px and CAT activities were higher in adult camels than in the young whereas no significant difference in the activity of SOD between young and adult camels was noticed. Glutathione was present in all tissues studied. Ascorbic acid was found to have significantly higher values in young camels. From this study it could be concluded that, as in other mammals, camel tissues contain a powerful antioxidant system. The liver has the highest contents of antioxidants and antioxidant enzymes indicating that it plays an important role in pro-oxidants detoxification. Age has a variable effect on the antioxidant system in camels.     

The Activities of Antioxidant Enzymes and the Glutathione Content of the Digestive Organs in Marine Invertebrates from Possiet Bay,Sea of Japan

The main components of the antioxidant (AO) system, that is, the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as the glutathione content of cells of the digestive organs, have been measured in 26 species of marine invertebrates that belong to four taxonomic groups from the Possiet Bay, Sea of Japan. It has been shown that the activities of antioxidant enzymes and glutathione content are species specific. In the digestive organs of echinoderms, the activities of antioxidant enzymes and the glutathione content are generally higher compared with those in mollusks. All the studied species exhibit the greatest variability in the activities of catalase and glutathione peroxidase; the lowest variability occurred in activities of superoxide dismutase and glutathione content. The possible causes of the differences in the levels of the investigated components of the AO system are discussed.     

Ontogenic characteristics of lipid peroxidation and antioxidant system enzymes in the brain of geese

Peculiarities of antioxidant homeostasis of geese brain tissue during embryogenesis and early postnatal period have been studied. It has been shown that the cerebrum and hindbrain tissues are characterized by a higher level of lipid peroxidation compared to liver. Main antioxidative enzymes' activity (superoxide dismutase, catalase, glutathione peroxidase) in the brain already reaches its maximum in the middle period of embryogenesis. We have found that brain tissues are characterized by a lower activity of intracellular enzymes (superoxide dismutase, catalase) but increased glutathione peroxidase activity as compared to liver. The rate of Fe2+ initialized lipid peroxidation and coefficient of antioxidative activity were used as a criterion for evaluation of antioxidative system's status. According to the dynamics of these factors the highest tension of antioxidative system in the brain appears in the period of the contour (28 days) and juvenile (49 days) feather formation.     

Seasonal variations in the antioxidant defence systems and lipid peroxidation of the digestive gland of mussels.

1. The seasonal variations in the level of antioxidant compounds (glutathione (GSH), vitamin E, carotenoids) and in the activity of antioxidant enzymes, superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), GSH-peroxidase (EC 1.11.1.9) in the digestive gland of mussels (Mytilus sp.) were evaluated. The lipid peroxidation process was also measured by determining the tissue concentration of malondialdehyde (MDA). 2. The physiological fluctuations of the antioxidant defence systems were inversely related to the accumulation of lipid peroxidation products (MDA) in the tissue. The observed seasonal variations are presumably related to the changing metabolic status of the animals, itself dependent on such factors as gonad ripening and food availability. 3. In particular, the obtained data indicate that a reduction of the antioxidant defence systems, occurring during winter, could be directly responsible for an enhanced susceptibility of mussels tissues to oxidative stress, as indicated by the high MDA concentration observed in this period.     

PprI和RecX蛋白对耐辐射奇球菌抗氧化作用的影响

利用基因突变、化学发光法和酶活性分析研究了耐辐射奇球菌中与辐射抗性密切相关的基因pprI(Dr0167)和recX(Dr1310)突变对菌体活性氧清除作用的影响,分析了其对抗氧化酶活性的调控功能。实验结果表明,缺失pprI的突变株对活性氧自由基氧化异常敏感,过氧化氢酶和超氧化物歧化酶活性显著降低。与之相反,RecX对菌体活性氧清除作用表现为一种“负”的影响,即缺失recX的突变株对活性氧自由基的清除能力反而增强了,过氧化氢酶和超氧化物歧化酶的酶活性明显增加。表明这两个基因与抗氧化系统的调控有关。为进一步研究该菌的抗氧化机制提供了一些思路。     

Lipoperoxides, vitamin E, and activities of superoxide dismutase, glutathione peroxidase, and catalase in regenerating rat liver

Lipoperoxides in homogenates of regenerating rat liver increased from 6 hours after the operation and reached a peak (about 7 times the control level) 18-24 hours after the operation. The concentration of blood lipoperoxides rapidly decreased after the operation. The enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase, and vitamin E content in regenerating livers were also determined. Among these antioxidant factors, the catalase level changed markedly.     

Effects of Chlorpromazine on the Activities of Antioxidant Enzymes and Lipid Peroxidation in the Various Regions of Aging Rat Brain

In this work, the effect of chronic intraperitoneal administration of chlorpromazine (5 and 10 mg/kg) on the antioxidant enzymes superoxide dismutase (SOD), catalase (CA), glutathione reductase (GR), and glutathione peroxidase (GP); lipid peroxidation; and lipofuscin accumulation in the brains of rats ages 6, 9, and 12 months was studied. Chlorpromazine increased the activities of SOD, GR, and GP in particulate fraction from cerebrum, cerebellum, and brain stem in a dose-dependent manner. While GR and SOD associated with soluble fraction increased, GP associated with soluble fraction was not affected. CA did not change after chlorpromazine administration in any regions of the brain of rats from all age groups. Chlorpromazine, thus, had a somewhat different action on antioxidant enzymes in different subcellular fractions. Chlorpromazine inhibited lipid peroxidation, both in vivo and in vitro, and it also inhibited accumulation of lipid peroxidation fluorescent products (lipofuscin), which was studied histochemically and biochemically as well. The data indicate that chlorpromazine inhibition of lipid peroxidation and of accumulation of lipofuscin can result from elevation of the activity of brain antioxidant enzymes.