Oxidative impairment in scrapie-infected mice is associated with brain metals perturbations and altered antioxidant activities

Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)). PrP(C) binds copper, has superoxide dismutase (SOD)-like activity in vitro, and its expression aids in the cellular response to oxidative stress. However, the interplay between PrPs (PrP(C), PrP(Sc) and possibly other abnormal species), copper, anti-oxidation activity and pathogenesis of prion diseases remain unclear. In this study, we reported dramatic depression of SOD-like activity by the affinity-purified PrPs from scrapie-infected brains, and together with significant reduction of Cu/Zn-SOD activity, correlates with significant perturbations in the divalent metals contents. We also detected elevated levels of nitric oxide and superoxide in the infected brains, which could be escalating the oxidative modification of cellular proteins, reducing gluathione peroxidase activity and increasing the levels of lipid peroxidation markers. Taken together, our results suggest that brain metal imbalances, especially copper, in scrapie infection is likely to affect the anti-oxidation functions of PrP and SODs, which, together with other cellular dysfunctions, predispose the brains to oxidative impairment and eventual degeneration. To our knowledge, this is the first study documenting a physiological connection between brain metals imbalances, the anti-oxidation function of PrP, and aberrations in the cellular responses to oxidative stress, in scrapie infection.     

Gene expression and activity of antioxidant enzymes in barley (Hordeum vulgare L.) under controlled severe drought

The objective of the present study was to determine the activity of antioxidant enzymes: superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) and the expression of their genes in two barley genotypes under controlled severe drought. To fulfill this objective, 21-day-old barley plants of two genotypes: Rum and Yarmouk were exposed to controlled severe drought (25% field capacity) for 2, 9, and 16 days. The activity of SOD was significantly high in Rum genotype after 2 days of drought treatment. In Yarmouk genotype, the activity of APX was significantly high after 2 and 9 days of drought treatment. In Rum genotype, CAT2 was upregulated after 9 days of drought treatment and SOD and APX were upregulated after 16 days of drought treatment, whereas CAT2, SOD, and APX were upregulated in Yarmouk genotype after 2 days of drought treatment. The results indicate a unique pattern of activity and gene expression of the antioxidant enzymes in the two barley genotypes under controlled severe drought. Moreover, the data suggest that each genotype utilizes different molecular and biochemical responses under the same drought conditions.     

Oxidative stress and antioxidant content in Chlorella vulgaris after exposure to ultraviolet-B radiation

Growth of Chlorella vulgaris was measured in cultures irradiated with 0, 0.8, 2.0 and 4.4 kJ m² UV-B. Growth expressed as chlorophyll content, declined significantly with increased UV-B dose. Ultraviolet-B irradiated cultures in log phase of growth showed a 284% increase in oxygen radical generation and a 145% increase in lipid peroxidation compared with unirradiated cultures, whereas cultures in the stationary growth phase showed no significant changes in these parameters. The activities of superoxide dismutase and catalase increased by 40 and 500%, respectively, after exposure to a UV-B dose of 4.4 kJ m⁻². Contents of the lipophilic antioxidants α-tocopherol and β-carotene increased by 180 and 63 amol cell⁻¹ respectively, between log and stationary phases in unirradiated cultures; but in UV-B-irradiated cultures these increases were significantly depressed. Photoreducing capacities of chloroplasts were decreased following UV-B irradiation of both isolated chloroplasts and those isolated from irradiated algae. Cells exposed to UV-B exhibited increased size and starch accumulation. These results suggest that oxidative stress conditions related to UV-B exposure trigger an antioxidant response that includes an increase in the activity of the antioxidant enzymes (superoxide dismutase and catalase).     

Effect of cadmium on lipid peroxidation and activities of antioxidant enzymes in growing pigs

Malondialdehyde (MDA), glutathione (GSH) content, total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were studied in serum, liver, and kidney of growing pigs after graded doses of cadmium administration in diets. One hundred ninety-two barrows (Duroc x Landrace x Yorkshire), with similar initial body weight 27.67±1.33 kg, were randomly allotted into 4 different treatments with 3 replications (16 pigs per replication). The treatments received the same basal diet added with 0, 0.5, 5.0, and 10.0 mg/kg cadmium (as CdCl₂), respectively. The results showed pigs treated with 10 mg/kg cadmium significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the control. In this treatment, the contents of MDA increased significantly (p<0.05), GSH concentrations, T-AOC levels, and the activities of SOD, GSH-PX, and GST decreased significantly (p<0.05). The results indicate 10 mg/kg cadmium could decrease pig antioxidant capacity after extended exposure and cadmium-induced increase lipid peroxidation might not be only the result of the possibility of lower level of GSH but could also be as a result of direct action of cadmium on peroxidation reaction.     

Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury

We studied the effect of glycine supplementation on lipid peroxidation and antioxidants in the erythrocyte membrane, plasma and hepatocytes of rats with alcohol-induced hepatotoxicity. Administering ethanol (20%) for 60 days to male Wistar rats resulted in significantly elevated levels of erythrocyte membrane, plasma and hepatocyte thiobarbituric acid reactive substances (TBARS) as compared with those of the experimental control rats. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) were also observed on alcohol supplementation as compared with those of the experimental control rats. Glycine was administered at a dose of 0.6 g kg(-1) body weight to rats with alcohol-induced liver injury, which significantly decreased the levels of TBARS and significantly elevated the activities of SOD, CAT, GSH, GPx and GR in the erythrocyte membrane, plasma and hepatocytes as compared to that of untreated alcohol supplemented rats. Thus, our data indicate that supplementation with glycine offers protection against free radical-mediated oxidative stress in the erythrocyte membrane, plasma and hepatocytes of animals with alcohol-induced liver injury.     

Exercise,depletion of antioxidants and antioxidant manipulation

Strenuous physical activity is known to increase the production of reactive oxygen species (ROS), associated with depletion of antioxidant defence. In the present work we evaluated the level of lipid peroxidation and antioxidant components in blood of sportsmen under resting conditions and compared the data obtained with those in age- and sex-matched sedentary controls. A significant increase was noted in the levels of thiobarbituric acid reactive substances (TBARS) and conjugated dienes while a decrease was observed in ascorbic acid and glutathione levels in sportsmen. α-Tocopherol was unaltered in plasma of sportsmen as compared to controls. The activity of superoxide dismutase was increased (52 per cent) and glutathione peroxidase was decreased (43 per cent) in the erythrocytes of sportsmen compared to controls. Basal glutathione levels were negatively correlated with conjugated dienes and maximal oxygen uptake (VO_2max) of the subjects. Dietary supplementation with antioxidant vitamins has been shown to be beneficial in combating oxidative stress without enhancing performance while exogenous glutathione was found to influence the endurance capacity of athletes. Such studies demonstrate the critical role played by glutathione and suggest that intervention trials should include a mixture of antioxidants rather than a single antioxidant. Copyright © 1998 John Wiley & Sons, Ltd.     

Effect of stress on the antioxidant enzymes and gastric ulceration

The effect of cold-restraint stress on the antioxidant enzymes of the rat gastric mucosa was studied with a view to finding out their role in stress induced gastric ulceration. Histological examination revealed stress induced extensive damage of the surface epithelial cell with lesions extending upto submucosa in some cases. Stress causes time-dependent increase in histamine and pepsin content but decrease in acid content of the gastric fluid with the progress of ulceration (ulcer index) for two hours. The tissue lipid peroxidation was significantly increased as evidenced by accumulation of malondialdehyde. Since lipid peroxidation results from the generation of reactive oxygen species, stress effect was studied on some antioxidant enzymes such as superoxide dismutase, peroxidases and prostaglandin synthetase as a function of time. The time dependent increase in stress ulcer correlates well with the concomitant increase in superoxide dismutase activity and decrease in peroxidase and prostaglandin synthetase activity. This creates a favourable condition for accumulation of endogenous H₂O₂ and more reactive hydroxyl radical (OH·). Administration of antioxidants such as reduced glutathione or sodium benzoate prior to stress causes significant decrease in ulcer index and lipid peroxidation and protection of gastric peroxidase activity suggesting the involvement of reactive oxygen species in stress induced gastric ulceration. This is supported by thein vitro observation that OH· can also inactivate peroxidase and induce lipid peroxidation. As prostaglandin is known to offer cytoprotection, stress-induced loss of prostaglandin synthetase activity appears to aggravate the oxidative damage caused by reactive oxygen species.Abbreviations ROS reactive oxygen species - GPO gastric peroxidase - SOD superoxide dismutase - MDA malondialdehyde - GSH reduced glutathione - TCA trichloroacetic acid     

Protective role of new nitrogen compounds on ROS/RNS-mediated damage to PC12 cells

Reactive oxygen (ROS) and nitrogen (RNS) species are known to be involved in many degenerative diseases. This study reports four new nitrogen compounds from organic synthesis, identified as FMA4, FMA7, FMA762 and FMA796, which differ mainly by the number of hydroxyl groups within their phenolic unit. Their potential role as antioxidants was evaluated in PC12 cells by assessing their protection against oxidative and nitrosative insults. The four compounds, and particularly FMA762 and FMA796, were able to protect cells against lipid peroxidation and intracellular ROS/RNS formation to a great extent. Their protective effects were likely mediated by their free radicals scavenging ability, as they appeared to be involved neither in the induction of natural antioxidant enzymes like GSH-PX and SOD, nor in the inhibition of NOS. Nevertheless, these results suggest a promising potential for these compounds as ROS/RNS scavengers in pathologies where oxidative/nitrosative stress are involved.     

Different antioxidants status, total antioxidant power and free radicals in essential hypertension

Hypertension is a multi-factorial process, prevalent in developed as well as in developing countries. Different antioxidants and free radicals play an important role in cardiovascular system. In present study, total antioxidant power in terms of FRAP (ferric reducing activity of plasma), free radicals and different antioxidants have been studied in essential hypertensives (n = 50) and normal subjects (n = 50). Levels of total cholesterol, low-density lipids-cholesterol, malonialdehyde, very low-density lipids (VLDL), uric acid, plasma homocysteine and low-density lipids (LDL), were significantly higher in hypertensives as compared to normotensive. HDL-cholesterol, SOD, GPx, reduced glutahione, total glutathione, oxidized glutathione, total thiols, protein thiols, non protein thiols, RNI, total antioxidant power, vitamin A, ascorbic acid and glutahione-S-transferase (GST) were decreased significantly in normotensive. We observed significantly low nitric oxide levels in hypertensive patients. No correlation was observed between severity of disease and plasma nitric oxide levels. There was a significant decrease in plasma FRAP value in essential hypertensives as compared to normotensive controls, which showed a negative correlation with diastolic blood pressure. In conclusion, our study revealed that there was a consistent significant difference between essential hypertensives versus controls with respect to most of the parameters. These complex changes are consistent in the view that essential hypertension is associated with an abnormal level of antioxidant status compared to normal response to oxidative stress or both.     

Chilling-induced changes in membrane fluidity and antioxidant enzyme activities in Coffea arabica L. roots

Exposure of coffee to low temperatures caused growth inhibition, changes in metabolic rates, and membrane alterations. Root tissue exposed to 10 °C evolved significantly lower rates of metabolic heat compared with controls grown at 25 °C, and the values were closely associated with the observed root growth inhibition. Electron paramagnetic resonance spectra of intact tissues showed that the spin probe 5-doxylstearic acid was capable to intercalate within the cellular membrane lipids. Indeed, at the depth of the 5th carbon atoms of the alkyl chains, the nitroxide radical detected more rigid membranes in seedlings exposed to 10 °C compared with 25 °C treated samples. Ascorbate peroxidase and catalase activities did not show appreciable changes under chilling conditions, while guaiacol peroxidase activity increased 55 % compared to the control. On the other hand, glutathione reductase activity decreased, in parallel to a significant decline in the capacity to reduce triphenyl-tetrazolium. Our results showed a marked correlation between lipid peroxidation and root tissue damage, which seemed to be associated with increased membrane rigidity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Antioxidant capacity of <Emphasis Type="Italic">Brassica juncea</Emphasis> plants exposed to elevated levels of copper

Brassica juncea L. eight-day-old seedlings treated with various concentrations (50–200 µM) of copper for 48 h accumulated Cu more in the roots than in leaves. Accumulation of copper resulted in more active lipid peroxidation and depletion of glutathione (GSH) pools in both roots and shoots, which was attributed to copper-induced additional oxidative stress. Activities of ascorbate peroxidase and superoxide dismutase were higher in both roots and shoots while catalase activity increased in leaves but remained unchanged in roots in response to copper accumulation. Changes in lipid peroxidation, GSH content, and antioxidant enzyme activities suggest that oxidative damage may be involved in copper toxicity.From Fiziologiya Rastenii, Vol. 52, No. 2, 2005, pp. 233–237.Original English Text Copyright © 2005 by Devi, Prasad.This article was submitted by the authors in English.This revised version was published online in April 2005 with a corrected cover date.     

Retinol supplementation induces oxidative stress and modulates antioxidant enzyme activities in rat Sertoli cells

Recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol caused cellular oxidative stress and modulated superoxide dismutase, catalase and glutathione peroxidase activities. Retinol (7 μM) significantly increased TBARS, conjugated dienes, and hydroperoxide-initiated chemiluminescence in cultured Sertoli cells. In response to retinol treatment superoxide dismutase, catalase and glutathione peroxidase activities increased. TBARS content and catalase activities were decreased by a free radical scavenger. These findings suggest that retinol may induce oxidative stress and modulate antioxidant enzyme activities in Sertoli cells.     

Effect of cigarette smoke on lipid peroxidation,antioxidant enzymes and NMDA receptor subunits 2A and 2B concentration in rat hippocampus

The effect of cigarette smoke on lipid peroxidation and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and on the concentration of N-methyl-d-aspartate receptor (NMDAR) subunits 2A and 2B in the hippocampus of Sprague-Dawley rats exposed to cigarette smoke for 2h/day for a period of 4 weeks was determined. It was observed that NMDAR 2A and 2B concentrations in the hippocampus were enhanced in the case of animals exposed to cigarette smoke, whereas lipid peroxidation and antioxidant enzyme activities did not show any change as compared to control animals. The results of our study suggest that cigarette smoke induces NMDAR 2A and 2B expression in the hippocampus, and that this is not due to an increased lipid peroxidation, because cigarette smoke has no effect on lipid peroxidation and antioxidant enzyme activities in the hippocampus.     

Peritrophic envelope as a functional antioxidant

The peritrophic envelope has long been considered an important microbial barrier to midgut infection and as a selective filter for the exclusion of dietary toxins. In this paper, we present data indicating that the peritrophic envelope (PE) of Helicoverpa zea serves as a functional antioxidant, protecting the midgut epithelium from damage by dietary prooxidants. Results from in vitro assays indicate that PE effectively scavenges hydroxyl radicals and reduces hydroperoxide formation in isolated midgut tissues exposed to model free radical generating systems. The extraordinary similarity in location and function of the PE to gastric mucins of vertebrates is discussed. © 1996 Wiley-Liss, Inc.     

Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury

Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The effect of pretreatment with aqueous black tea extract on lipid peroxidation and antioxidants in the liver was investigated. Administering a combination dose of chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate days over a 15-day period to male mice resulted in induction of sub-acute toxicity as reflected by elevated levels of liver damage marker enzymes alkaline phosphatase(ALP), aspartate transaminase(AST) and alanine transaminase(ALT). Significantly elevated levels of lipid peroxidation were observed in the experimental group (group III) as compared with control mice. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total thiol, glutathione peroxidase (GPx), glutathione reductase(GR) and glutathione-S-transferase (GST) were also observed in pesticide-treated as compared to control mice. Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls. Thus, the data offer support for the claim that the central mechanism of pesticide action occurs via changes in cellular oxidative status and shows conclusively that supplementation with black tea extract protects against the free radical-mediated oxidative stress in hepatocytes of animals with pesticide-induced liver injury.     

Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy

Earlier we reported that probucol treatment subsequent to the induction of diabetes can prevent diabetes-associated changes in myocardial antioxidants as well as function at 8 weeks. In this study, we examined the efficacy of probucol in the reversal of diabetes induced myocardial changes. Rats were made diabetic with a single injection of streptozotocin (65 mg/kg, i.v.). After 4 weeks of induction of diabetes, a group of animals was treated on alternate days with probucol (10 mg/kg i.p.), a known lipid lowering agent with antioxidant properties. At 8 weeks, there was a significant drop in the left ventricle (LVSP) and aortic systolic pressures (ASP) in the diabetic group. Hearts from these animals showed an increase in the thiobarbituric acid reacting substances (TBARS), indicating increased lipid peroxidation. This was accompanied by a decrease in the myocardial antioxidant enzymes activities, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). Myocardial catalase activity in the diabetic group was higher. In the diabetic + probucol group both LVSP and ASP showed significant recovery. This was also accompanied by an improvement in SOD and GSHPx activities and there was further increase in the catalase activity. Levels of the TBARS were decreased in this group. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit which can be reversed with probucol treatment. Improved cardiac function with probucol may be due to the recovery of antioxidants in the heart.     

Salt stress regulates enzymatic and nonenzymatic antioxidative defense system in the edible part of carrot (Daucus carota L.)

Carrot (Daucus carota L.) is widely utilized all over the world due to its enriched healthy nutritional composition. However, its growth and quality is adversely affected due to saline stress. To assess salt-induced regulation in different enzymatic and nonenzymatic antioxidants in the edible part of two cultivars (T-29 and DC-4) of carrot, a greenhouse experiment was conducted. The cultivars were grown for 90 days under varying (0, 50, 100, and 150 mM NaCl) saline regimes. High accumulation of glycinebetaine (GB), malondialdehyde (MDA), and ascorbic acid (AsA) contents was found in the roots of both carrot lines under varying saline regimes. However, total soluble proteins and activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) declined in the edible part of both carrot cultivars. Alpha-tocopherol (α-Toco) contents remained almost unaffected at all saline regimes except at 150 mM NaCl, where tocopherol content increased markedly. Of both carrot cultivars, cv. DC-4 accumulated relatively higher amount of GB, soluble protein and α-Toco contents than cv. T-29. The cv. T-29 had considerably higher amounts of AsA and MDA and activities of POD, SOD, and CAT than those in cv. DC-4 both under saline and nonsaline conditions. Overall, GB, AsA, and MDA contents increased while enzymatic antioxidant activities decreased in both carrot cultivars under different saline regimes which indicated that the enzymatic antioxidant metabolism was negatively influenced in the edible part of carrot due to salinity stress. So it can be suggested that the carrot is salt sensitive and its nutritional value in terms of antioxidants declines under salt stress.     

Cadmium effects on growth and antioxidant enzymes activities in Miscanthus sinensis

Plants of Miscanthus sinensis (cv. Giganteus) were grown in hydroponics for three months in nutrient solution with 0, 2.2, 4.4 and 6.6 μM CdNO₃. Growth parameters, catalase (CAT), guaiacol peroxidase (POD), ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities were analysed in leaves and roots collected after 1-and 3-month exposure. Dry biomass of all miscanthus organs was affected by Cd concentration both after 1-and 3-month exposure. No visible symptoms of Cd toxicity were observed in shoots and rhizomes of plants grown in presence of Cd. In contrast, roots became shorter and thicker and the whole root system more dense and compact already after one month of treatment with 6.6 μM Cd. The lower Cd concentration increased the enzymes activities after 3 months in leaves and only after 1-month in roots, while a decrease in activity was observed at higher Cd concentrations.     

Large‐brained birds suffer less oxidative damage

Large brains (relative to body size) might confer fitness benefits to animals. Although the putative costs of well‐developed brains can constrain the majority of species to modest brain sizes, these costs are still poorly understood. Given that the neural tissue is energetically expensive and demands antioxidants, one potential cost of developing and maintaining large brains is increased oxidative stress (‘oxidation exposure’ hypothesis). Alternatively, because large‐brained species exhibit slow‐paced life histories, they are expected to invest more into self‐maintenance such as an efficacious antioxidative defence machinery (‘oxidation avoidance’ hypothesis). We predict decreased antioxidant levels and/or increased oxidative damage in large‐brained species in case of oxidation exposure, and the contrary in case of oxidation avoidance. We address these contrasting hypotheses for the first time by means of a phylogenetic comparative approach based on an unprecedented data set of four redox state markers from 85 European bird species. Large‐brained birds suffered less oxidative damage to lipids (measured as malondialdehyde levels) and exhibited higher total nonenzymatic antioxidant capacity than small‐brained birds, whereas uric acid and glutathione levels were independent of brain size. These results were not altered by potentially confounding variables and did not depend on how relative brain size was quantified. Our findings partially support the ‘oxidation avoidance’ hypothesis and provide a physiological explanation for the linkage of large brains with slow‐paced life histories: reduced oxidative stress of large‐brained birds can secure brain functionality and healthy life span, which are integral to their lifetime fitness and slow‐paced life history.     

氯化钠胁迫对嫁接茄子生长、抗氧化酶活性和活性氧代谢的影响

以日本引进的茄子设施栽培专用耐盐品种‘Torvum Vigor’为砧木,栽培品种‘苏崎茄’为接穗,在营养液栽培条件下,对80 mmol·L^-1 NaCl胁迫下茄子嫁接苗和自根苗的光合特性、叶片抗氧化酶活性、活性氧代谢进行了比较.结果表明：NaCl胁迫下,茄子嫁接苗的干质量、叶绿素含量和光合速率分别比苏崎茄自根苗高67。8％、8。8％和31。1％,均有显著差异;抗氧化酶活性均显著高于苏崎茄自根苗,而O₂^-_·生成速率、H₂O₂和MDA含量则显著低于苏崎茄自根苗.NaCl胁迫明显降低了叶片叶绿素含量和光合速率,显著增加了O₂^-_·生成速率、H₂O₂和MDA含量,但嫁接苗受NaCl胁迫的影响小于苏崎茄自根苗,嫁接苗较强的耐盐性与NaCl胁迫下较高的抗氧化酶活性和较低的氧化损伤有关.