Decreased Glutathione Peroxidase Research Articles

Interplay of TNF-α and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes

Oxidative stress and inflammation are considered to be important factors in the pathogenesis of congestive heart failure subsequent to myocardial infarction. Endogenous TNF-α plays a central role in initiating and sustaining the inflammatory response. IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-α. In this study, we tested whether an imbalance of these two contrasting cytokines leads to increased oxidative stress and cardiac myocyte dysfunction. Isolated adult rat cardiac myocytes were exposed to different concentrations of TNF-α and IL-10 (1–20 ng/ml) alone or in combination. As a positive control, cells were also exposed to H 2O 2 (100 μÌ) to induce oxidative stress. An exposure to TNF-α (10 ng/ml) caused a significant decrease in both protein and mRNA for manganese superoxide dismutase and catalase, decreased glutathione peroxidase protein, increased intracellular reactive oxygen species and lipid peroxidation, and caused cell injury as measured by creatine kinase release. IL-10 treatment (10 ng/ml) by itself had no effect on any of these parameters, but it prevented all the above listed changes caused by TNF-α. IL-10/TNF-α ratio of lower or higher than 1 was less effective in reducing TNF-α generated oxidative stress. H 2O 2 treatment increased oxidative stress and cell injury and TNF-α mimicked these effects. This study suggests that a proper balance between IL-10 and TNF-α, rather than any of the individual cytokines is of more physiological importance in mediating oxidative-stress-induced cardiac injury.

Antioxidant effect of diphenyl diselenide against sodium nitroprusside (SNP) induced lipid peroxidation in human platelets and erythrocyte membranes: An in vitro evaluation

An in vitro evaluation on the antioxidant effect of diphenyl diselenide (PhSe)(2), an organochalcogenide, against sodium nitroprusside (SNP)-induced lipid peroxidation (LPO) was conduced. Human platelets and erythrocyte membranes (ghosts), as well as rat brain homogenates (S(1)), were pre-incubated with different concentrations of SNP (0-10 microM). All SNP concentrations tested significantly increased LPO in human platelets and S(1). Platelets were more sensitive to SNP-induced peroxidative damage when compared to S(1). SNP 10 microM decreased glutathione peroxidase (GPx) activity and did not affect glutathione reductase (GR) and catalase (CAT) activities in human platelets. However, ghosts were insensitive to SNP-induced LPO and no changes on GPx, GR and CAT activities were observed. Diphenyl diselenide significantly protected human platelets against SNP-induced LPO and recovered GPx inactivation. This effect was more evident at (PhSe)(2) concentrations above 2 microM. The presented results indicate that (PhSe)(2) exerts protective effects on SNP-induced oxidative damage in human blood components and in rat brain. These phenomena seem to be related to its thiol peroxidase-like activity and to a possible direct interaction with SNP and derivatives. Based on our results and on literature, diphenyl diselenide can be pointed as a promising antioxidant molecule.

Comparison of the effects of melatonin and pentoxifylline on carbon tetrachloride-induced liver toxicity in mice

The purpose of the study was to determine whether along and in combination melatonin (MLT) and pentoxifylline (PTX) exerted beneficial effects on histopathological changes and changes in oxidant and antioxidant systems in liver caused by CCl4-induced liver toxicity in mice. Mice were randomly divided into six groups: control, olive oil, toxicity, MLT, PTX, PTX+MLT. MLT 10 mg/kg/day, PTX 50 mg/kg/day, and the same individual doses in MLT+PTX combination were given intraperitoneally to mice for 7 day. CCl4 0.8 mg/kg/day was administered on the 4th, 5th, and 6th days of therapy in all groups except the control and olive oil groups. In the toxicity group, increased concentrations of malondialdehyde (MDA) and lipid hydroperoxides (LOOH) and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found compared to the control and olive oil groups (p < 0.05). Compared to the toxicity group, both the PTX group and the PTX+MLT group had decreased MDA and LOOH levels, whereas MLT reduced only LOOH levels (p < 0.01). MLT, PTX and MLT+PTX increased the GSH-Px and CAT activities compared to the toxicity group (p < 0.05). MLT increased CAT activity compared to PTX and MLT+PTX (p < 0.05). Superoxide dismutase enzyme activity did not change in any group (p < 0.05). Histopathologically, ballooning, degeneration, apoptosis, and bridging necrosis were seen in the toxicity group. MLT, PTX and MLT+PTX decreased the apoptosis and bridging necrosis (p < 0.01), and PTX and MLT+PTX decreased balloon degeneration compared to the toxicity group (p < 0.01). These results indicate that administration of PTX and MLT alone and in combination before onset of liver toxicity might prevent the oxidative damage by reducing oxidative stress and increasing antioxidant enzyme levels.

Protective effect of crude extract from Wedelia paludosa (Asteraceae) on the hepatotoxicity induced by paracetamol in mice

Several in-vitro and in-vivo ethnopharmacological studies carried out with plants of the genus Wedelia have already demonstrated hepatoprotective effects in chemically-induced liver injury, including those induced by paracetamol. Here, the effects of the crude extract from Wedelia paludosa on paracetamol-induced hepatotoxicity in mice was investigated. Intraperitoneal injection of paracetamol (1,000 mg kg(-1)) caused 80% death after 24 h in mice, which was significantly reduced by oral pretreatment with W. paludosa (500 mg kg(-1)). Hepatotoxicity was observed 24 h after an intraperitoneal injection of paracetamol (600 mg kg(-1)), as evidenced by an increase in plasma activity of aspartate and alanine aminotransferases. That hepatotoxicity was significantly attenuated by W. paludosa pretreatment (100-500 mg kg(-1)) in a dose-response manner. Paracetamol (1,000 mg kg(-1)) drastically depleted total glutathione levels and decreased glutathione peroxidase and delta-aminolevulinate dehydratase activity in the liver, such effects not being prevented by pretreatment with W. paludosa. Neither paracetamol treatment alone nor pretreatment with W. paludosa altered glutathione reductase and glutathione S-transferase activity or the levels of end-products of lipid peroxidation. In conclusion, we found that W. paludosa protected against paracetamol-induced hepatotoxicity, an effect not observed over oxidative stress-related parameters. Hepatoprotection is likely mediated by some terpenes present in W. paludosa extract. However, further studies will be required to explain the mechanisms involved in the hepatoprotection afforded by W. paludosa.

Reactive oxidant species in asthma

This overview summarizes some recent studies on the balance of oxidants to antioxidants in patients with asthma. The aim of the review is to compare studies on the changes in oxidants/antioxidants in stable asthma or in acute exacerbation of asthma. Our review of the recent literature in this field seems to indicate conflicting findings. Increased release of reactive oxygen species such as superoxide anion and hydrogen peroxide has been reported in exhaled breath condensates and from circulating granulocytes, and from the bronchoalveolar lavage cells of patients with asthma. In asthma, bronchial obstruction is associated with an increased spontaneous and stimulus-induced production of oxygen free radicals. The primary defense against reactive oxygen species is endogenous antioxidants, which are found to be altered in asthma. A marked decrease in plasma antioxidant capacity occurs. Superoxide dismutase activity is higher in erythrocytes and serum of asthmatic than in normal subjects and is diminished in cells from lavage and brushing samples of patients with asthma. Higher level of erythrocyte catalase activity has only been found in Chinese asthmatic patients while decreased glutathione peroxidase activity has been well documented. Since there are considerable discrepancies in erythrocyte or plasma antioxidant enzyme activity in patients with asthma, the problem at this time is attempting to sort out these conflicting results and to find their roles in the pathogenesis of asthma. There is good evidence that antioxidant compounds may have a potential role in the treatment of asthma, especially of asthma exacerbation.

The role of thioredoxin reductase activity in selenium-induced cytotoxicity

The selenoprotein thioredoxin reductase is a key enzyme in selenium metabolism, reducing selenium compounds and thereby providing selenide to synthesis of all selenoproteins. We evaluated the importance of active TrxR1 in selenium-induced cytotoxicity using transfected TrxR1 over-expressing stable Human Embryo Kidney (HEK-293) cells and modulation of activity by pretreatment with low concentration of selenite. Treatment with sodium selenite induced cytotoxity in a dose-dependent manner in both TrxR1 over-expressing and control cells. However, TrxR1 over-expressing cells, which were preincubated for 72 h with 0.1 μM selenite, were significantly more resistant to selenite cytotoxicity than control cells. To demonstrate the early effects of selenite on behaviour of HEK-293 cells, we also investigated the influence of this compound on cell motility. We observed inhibition of cell motility by 50 μM selenite immediately after administration. Moreover, TrxR1 over-expressing cells preincubated with a low concentration of selenite were more resistant to the inhibitory effect of 50 μM selenite than those not preincubated. It was also observed that the TrxR over-expressing cells showed higher TrxR1 activity than control cells and the preincubation of over-expressing cells with 0.1 μM selenite induced further significant increase in the activity of TrxR1. On the other hand, we demonstrated that TrxR1 over-expressing cells showed decreased glutathione peroxidase activity compared to control cells. These data strongly suggest that TrxR1 may be a crucial enzyme responsible for cell resistance against selenium cytotoxicity.

Prooxidant-Antioxidant Balance in the Prostate and Blood of Rats with Sulpyride-Induced Prostatic Hyperplasia Corrected with Prostatilen

We studied the effects of 30-day injections of sulpyride and treatment with Prostatilen on the development of prostatic hyperplasia and LPO in rats. Sulpyride induced proliferation of lateral lobes, increased the content of lipid hydroperoxides and glutathione peroxidase activity in the gland; in the blood this preparation increased lipid hydroperoxide concentration and decreased glutathione peroxidase and total antioxidant activity. Prostatilen prevented the development of hyperplasia and normalized the prooxidant-antioxidant balance in tissues, except total antioxidant activity of the blood.

Effects of N-nitro l-arginine methyl ester (l-NAME), a potent nitric oxide synthase inhibitor, on visual evoked potentials of rats exposed to different experimental stress models.

The aim of our study was to investigate the effects of the nitric oxide synthase inhibitor, N-nitro l-arginine methyl ester (l-NAME, 10 mg kg-1 day-1 i.p.), on visual evoked potentials (VEPs) and lipid peroxidation expected to occur during chronic stress (15 days). Eight experimental groups, each consisting of 10 rats, were formed: control group (C), the group injected with l-NAME (L), groups exposed to cold stress (CS), immobilization stress (IS), and both cold and immobilization stress (CIS), groups exposed to stress and injected with l-NAME (CSL, ISL, CISL). l-NAME decreased brain and retina nitrite levels in all experimental groups compared with their corresponding control groups. l-NAME decreased glutathione peroxidase (GSH-Px) activity in the brain and retina in the L group, but increased it in the CSL and CISL groups compared with the C group. Lipid peroxidation was increased in the brain and retina tissues of all stress groups with respect to the C group. l-NAME markedly increased brain thiobarbituric acid reactive substances (TBARS) levels in the L group, while significantly decreasing brain and retina TBARS levels in all stress groups in comparison with their respective control groups. l-NAME caused a significant delay in all components of VEPs in the L group compared with the C group. However, l-NAME significantly decreased latencies of P1, N1, P2 and P3 components in the CSL group and all components in the ISL and CISL groups with respect to their corresponding control groups. This study clearly indicated that lipid peroxidation may be one possible factor affecting VEP components.

Binge ethanol exposure increases liver injury in obese rats

Background & Aims : The objective of this study was to address the hepatic effects of acute alcohol consumption in obesity by simulating an alcohol binge in genetically obese fa/fa rats compared with lean Fa/? rats. Methods : Ethanol 4 g/kg or saline was administered by gavage every 12 hours for 3 days. Results : Plasma alcohol levels were similar in both groups. Binge ethanol exposure caused liver injury in obese fa/fa but not in lean Fa/? rats, as assessed by alanine aminotransferase and H&E staining. Obesity impaired the antioxidant defense because basal levels of glutathione, glutamate cysteine ligase modulatory subunit, catalase, glutathione reductase, and superoxide dismutase were lower in fa/fa compared with Fa/? rats; the ethanol binge further decreased these antioxidants in fa/fa rats and also decreased glutathione peroxidase activity. Nonesterified fatty acids and lipid peroxidation were increased after ethanol treatment in fa/fa rats. Cytochrome P450 2E1 was down-regulated in fa/fa compared with Fa/? rats; however, the ethanol binge increased cytochrome P450 2E1 in both genotypes. Adenosine triphosphate decreased and uncoupling protein 2 increased in fa/fa rats treated with ethanol. 3-Nitrotyrosine protein adducts were detected only in fa/fa rats treated with ethanol, and this was accompanied by an induction of inducible nitric oxide synthase. Ethanol binge increased caspase-3 and caspase-8 activity, the expression of Fas ligand, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling in fa/fa rats. Conclusions : These data indicate that binge drinking increases apoptosis and liver injury in obese rats more than in lean controls and suggest that the injury may involve oxidative and nitrosative damage.

Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout ( Oncorhynchus mykiss)

The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout ( Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), l-buthionine sulfoximine ( l-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC 50 366 μM) and cortisol secretion (EC 50 19 μM) in a concentration-related manner. Pretreatment with ATA and l-BSO enhanced the toxicity of endosulfan (LC 50 and EC 50, respectively, 302 and 2.6 μM with ATA, 346 and 3.1 μM with l-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC 50 of endosulfan to 51 μM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with l-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and l-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress.

Ebselen protects against methylmercury-induced inhibition of glutamate uptake by cortical slices from adult mice

Methylmercury (MeHg) is a highly neurotoxic compound and the inhibition of glutamate uptake by astrocytes has been pointed as an important mechanism involved in MeHg-induced glutamate excitotoxicity. We examined the effect of oral exposure to MeHg (10 and 40 mg/l in drinking water) on glutamate uptake by brain cortical slices of adult mice. Moreover, the possible protective role of ebselen (20 mg/kg, subcutaneously) against MeHg effect was also examined. In addition, it was measured the glutathione peroxidase and catalase activities in mice brain. Our results demonstrated, for the first time, that in vivo exposure to MeHg causes a dose-dependent decrease in glutamate uptake and that ebselen, which did not affect the uptake per se, reverted this effect. MeHg decreased glutathione peroxidase activity and increased catalase activity, effects which were also prevented by ebselen. These results may indirectly indicate that: (i) the in vivo inhibitory effect of MeHg on glutamate uptake could be probably related to overproduction of H 2O 2; (ii) the protective effect of ebselen on MeHg-induced inhibition of glutamate uptake could be related to its ability to detoxify H 2O 2.

Antioxidant activity of Smoke Shield in-vitro and in-vivo.

Smoke Shield is a proprietory formulation containing extract of turmeric (Curcuma longa), obtained by supercritical carbon dioxide gas extraction and post-supercritical hydroethanolic extraction, together with extracts of green tea and other spices whose presence synergistically increases the activity of turmeric. This study evaluates the antioxidant potentials of Smoke Shield in-vitro and in experimental animals, as well as in human models. Smoke Shield was found to scavenge superoxide radicals generated by photoreduction of riboflavin (50% inhibitory concentration = 91 microg mL(-1)) and hydroxyl radicals generated by Fenton reaction (50% inhibitory concentration = 95 microg mL(-1)) and reduced lipid peroxidation. Administration of Smoke Shield to mice was found to elevate antioxidant enzymes such as catalase and superoxide dismutase in blood as well as in liver and kidney. Glutathione-S-transferase activity was found to be significantly elevated in liver and kidney of animals treated with Smoke Shield. Glutathione levels were also significantly elevated in blood. Glutathione reductase was significantly elevated in kidney. Administration of Smoke Shield decreased the lipid peroxidation in serum, liver and kidney, as well as reduced the levels of conjugated dienes and hydroperoxides. Administration of Smoke Shield to smokers was found to increase the superoxide dismutase and glutathione in blood and decrease glutathione peroxidase. Smoke Shield inhibited phase I enzymes as represented by aniline-hydroxylase and aminopyrenedemethylase in-vitro. These results indicate that Smoke Shield has potent antioxidant activity, could inhibit phase I enzymes and increase detoxifying enzymes, which makes it an effective chemoprotective herbal formulation.

In vitro effects of selenite and mercuric chloride on liver thiobarbituric acid–reactive substances and non-protein thiols from rats: Influences of dietary cholesterol and polyunsaturated and saturated fatty acids

Objective We measured the in vitro effects of mercuric chloride (Hg 2+) and selenite (Se 4+) on hepatic 2-thiobarbituric acid–reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. Methods Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 μM) and sodium selenite (25 μM) for 1 h. Results The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil ( P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se 4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg 2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se 4+ and Hg 2+ chloride that after exposure to Se 4+ alone, suggesting an interaction between Hg 2+ and Se 4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. Conclusion Together these results indicated that the protective effect of Se 4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.

The effect of vitamin E on stress-induced changes in visual evoked potentials (VEPs) in rats exposed to different experimental stress models.

The aim of the study was to investigate the effects of vitamin E on stress-induced changes in visual evoked potentials (VEPs) and lipid peroxidation. Eight experimental groups of 10 rats per group were formed. These consisted of the control group (C); the group treated with vitamin E (E); groups exposed to cold stress (CS), immobilization stress (IS) and both cold and immobilization stress (CIS), and groups exposed to equivalent stresses and treated with vitamin E (CSE, ISE, CISE). Vitamin E was injected intramuscularly in a dose of 30 mg/kg/day. Following chronic stress (15 days), plasma corticosterone concentrations in all experimental groups were significantly increased over those in C group. Vitamin E significantly decreased corticosterone levels in all stress groups compared with their respective control groups. Brain nitrite levels were significantly more elevated in all stress groups than in the C group. Vitamin E reduced retina and brain nitrite levels in all stress and E groups compared with their respective control groups. Vitamin E decreased glutathione peroxidase (GSH-Px) activity in retina and brain tissues in the CSE group, but increased it in the ISE group compared with their respective control groups. Lipid peroxidation was increased in brain and retina tissues in all stress groups as indicated by the significant increase in thiobarbituric acid-reactive substance (TBARS) levels with respect to the C group. Vitamin E produced a significant decrease in brain and retina TBARS levels in all stress groups with respect to their corresponding control groups. The mean latencies of P1, N1, P2, N2 and P3 components were significantly prolonged in all stress groups compared with the C group. Vitamin E returned the VEP latencies in the stress groups to control values. Our findings clearly indicated that vitamin E has the potential to prevent VEP changes caused by stress.

Differential effect of dietary selenium on the long-term neurotoxicity induced by MDMA in mice and rats

We examined the effect of dietary selenium (Se) on the long-term effect of 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and 5-hydroxytryptamine (5-HT) containing neurons in the brain of mice and rats. Animals were fed either a Se-deficient (<0.02 ppm) or Se-replete (0.2 ppm) diet for 8 weeks. On the seventh week mice received three injections of MDMA (15 mg/kg, i.p. 3 h apart) or saline and rats a single dose of MDMA (12.5 mg/kg i.p.) or saline. All animals were sacrificed 7 days later. MDMA administration to mice depleted striatal DA concentration in both dietary groups, although depletion was considerably larger in the Se-deficient mice (64%) than Se-replete mice (30%). In addition, a decrease in 5-HT (17–32%) occurred in brain regions of Se-deficient but not Se-replete mice. In rats, MDMA decreased cortical [ 3H]-paroxetine binding (62%) and 5-HT content, the depletion being similar in the Se-deficient and Se-replete groups. No DA loss occurred in either group. There was no difference in the hyperthermic response induced by MDMA in Se-deficient or Se-replete animals. The Se-deficient diet decreased glutathione peroxidase (GPx) activity by 30% in mouse striatum and cortex and increased the degree of lipid peroxidation in cortical synaptosomes. Se-deficient rats also showed a decrease in brain GPx activity compared with the Se-replete group, but the degree of lipid peroxidation in synaptosomes was similar in both dietary groups. These results suggest that the antioxidant capacity of rats and mice differ leading to a differential susceptibility to the oxidative stress caused by MDMA in situations of low dietary Se.

Changes in somatosensory evoked potentials, lipid peroxidation, and antioxidant enzymes in experimental diabetes: effect of sulfur dioxide.

The effect of sulfur dioxide (SO2) on brain antioxidant status, lipid peroxidation, and somatosensory evoked potentials (SEPs) was investigated in diabetic rats. A total of 40 rats were divided into 4 equal groups: control (C), SO2 + C (SO2), diabetic (D), and SO2 + D (DSO2). Experimental diabetes mellitus was induced by i.v. injection of alloxan at a dose of 50 mg/kg body weight. Ten ppm SO2 was administered to the rats in the sulfur dioxide groups (SO2 and DSO2) in an exposure chamber. Exposure occurred 1 hr/day, 7 days/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. Although SO2 exposure markedly increased copper, zinc Superoxide dismutase activity, it significantly decreased glutathione peroxidase activity in both the diabetic and nondiabetic groups, compared with the C group. Brain catalase activity was unaltered; however, brain thiobarbituric acid reactive substances (TBARS) were elevated in all experimental groups with respect to the C group. SEP components P1, N1, P2, and N2 were significantly increased in all experimental groups, compared with the C group, and these components were also prolonged in the DSO2 group with respect to the other groups. The authors' findings suggest that exposure to SO2, because it increases lipid peroxidation, can change antioxidant enzyme activities and affect SEP components in diabetic rats.

Increased oxidative stress and altered levels of antioxidants in asthma

Background: Reactive oxygen species might play an important role in the modulation of airway inflammation. There is evidence of an oxidant-antioxidant imbalance in asthma. Although several oxidants and antioxidants are likely to be involved, alterations in only limited parameters have been studied in isolation. Objective: We investigated changes in a wide range of oxidants and antioxidants to create a comprehensive picture of oxidant-antioxidant imbalance. Methods: In the peripheral blood of 38 patients with bronchial asthma and 23 control subjects, oxidative stress was measured in terms of superoxide anion generation by leukocytes, lipid peroxidation products, total nitrates and nitrites, total protein carbonyls, and total protein sulfhydrils in plasma. Antioxidant status was evaluated by measuring red blood cell superoxide dismutase and catalase activity, total blood glutathione, and glutathione peroxidase activity in red blood cells and leukocytes and total antioxidant capacity in plasma. Results: Asthmatic patients showed increased superoxide generation from leukocytes, increased total nitrites and nitrates, increased protein carbonyls, and increased lipid peroxidation products and decreased protein sulfhydrils in plasma, indicating increased oxidative stress. They also showed increased superoxide dismutase activity in red blood cells and increased total blood glutathione and decreased glutathione peroxidase activity in red blood cells and leukocytes. Red blood cell catalase activity and the total antioxidant capacity of plasma were not altered. Conclusion: There are alterations in a wide array of oxidants and antioxidants, with balance shifting toward increased oxidative stress in asthma. Therapeutic augmentation of the antioxidant defenses might be beneficial. (J Allergy Clin Immunol 2003;111:72-8.)

Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and liver antioxidant status in mice: influence of ambient temperature.

The consumption of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is known to cause severe hyperthermia and liver damage in humans. The thermogenic response induced by MDMA is complex and partially determined by the prevailing ambient temperature (AT). This is of extreme importance since ecstasy is often consumed at "rave" parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. In view of the fact that hyperthermia is a well-known pro-oxidant aggressive condition, its potential role in ecstasy-induced hepatocellular toxicity should be further studied. Thus, the present study was performed in order to evaluate the influence of AT on the effects of single administration of MDMA on body temperature and liver toxicity in Charles River mice. Animals were given an acute intraperitoneal dose of MDMA (5, 10 or 20 mg/kg) and placed in AT of 20+/-2 degrees C or 30+/-2 degrees C for 24 h. Body temperature was measured during the study using implanted transponders and a temperature probe reading device. Plasma and liver samples were used for biochemical analysis. Liver sections were also taken for histological examination. The parameters evaluated were (1) plasma levels of transaminases and alkaline phosphatase, (2) hepatic glutathione (GSH), (3) hepatic lipid peroxidation, (4) activity of hepatic antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, glutathione- S-transferase, copper/zinc superoxide dismutase and manganese superoxide dismutase), and (5) liver histology. The hyperthermic response elicited by MDMA was clearly dose-related and potentiated by high AT. Administration of MDMA produced some evidence of oxidative stress, expressed as GSH depletion at both ATs studied, as well as by lipid peroxidation and decreased catalase activity at high AT. High AT, by itself, decreased glutathione peroxidase activity. Histological examination of the liver revealed abnormalities of a dose- and AT-dependent nature. These changes included vacuolation of the hepatocytes, presence of blood clots and loss of typical hepatic cord organisation. The results obtained in the present study suggest that oxidative stress plays a part in the first stage of MDMA-induced liver damage and that liver antioxidant status is aggravated by increased AT. Thus, these findings are in accordance with the hypothesis that high AT may potentiate ecstasy-induced hepatotoxicity by increasing body hyperthermia.

The influence of calcium channel blockers on the brain free fatty acid level and glutathione peroxidase activity in rats with lithium and pilocarpine‐induced status epilepticus

AbstractThe aim of this study was to investigate possible therapeutic approach to neuronal damage caused by status epilepticus. The effects of the L‐type voltage‐sensitive calcium channel blockers (nimodipine, nicardipine) and NMDA blockers (ifenprodil and MK‐801) on the brain free fatty acid (FFA) level and glutathione peroxidase (GPX) activity in rats with lithium and pilocarpine (LiPi) ‐ induced status epilepticus were examined. Vehicle or various doses of calcium channel and NMDA blockers had been injected i.p. 30 min after the pilocarpine application. Tested doses of nicardipine and MK‐801 did not influence the increase in the brain FFA level. Nimodipine and ifenprodil revealed a tendency to reduce FFA level. The inhibition of L‐type voltage‐sensitive Ca2+ channels or NMDA receptor ‐ associated channels was not sufficient for significant attenuation of an increase in the rat brain FFA content and a decrease GPX activity associated with LiPi ‐ induced status epilepticus. Individual compounds have shown to prevent FFA increase, suggesting some alternative or additional mechanism of action. The prevention of FFA accumulation was not followed by the prevention of GPX decrease indicating the activation of non FFA‐related mechanisms of cell damage.

Cyto-protective and immunomodulating properties of Amla ( Emblica officinalis) on lymphocytes: an in-vitro study

The fruits extracts of Emblica officinalis (Amla) has been reported to have strong anti-oxidant properties. There is a paucity of studies on the immunomodulatory properties of fruit extracts of Amla in immuno-compromised states, with the emphasis on lymphocytes. Therefore, the aim of the study was to determine the anti-oxidant and immunomodulatory properties of Amla using chromium (VI) as an immunosuppressive agent. Chromium (Cr) treatment results in enhanced cytotoxicity, free radical production, lipid peroxidation and decreased glutathione peroxidase (GPx) activity and diminished glutathione (GSH) levels. There was a significant inhibition of both lipopolysaccharide and concanavalin-A-stimulated lymphocyte proliferation. Chromium also inhibited Con A stimulated interleukin-2 and γ-interferon production significantly. Further, there was enhanced apoptosis and DNA fragmentation in the presence of Cr. Amla significantly inhibited Cr-induced free radical production and restored the anti-oxidant status back to control level. Amla also inhibited apoptosis and DNA fragmentation induced by Cr. Interestingly, Amla relieved the immunosuppressive effects of Cr on lymphocyte proliferation and even restored the IL-2 and γ-IFN production considerably.