Antioxidant system in Uromastyx philbyi during hibernation and activity periods

Hibernation is an extreme physiological state characterized by profound decreases in oxidative metabolism and body temperature during bouts of prolonged torpor, interrupted by brief periods of arousal with sudden increases in oxidative metabolism, with alterations in antioxidant defenses. We monitored the activities of antioxidant enzymes and oxidative stress during hibernation and activity in Uromastyx philbyi. 20 animals were used, 10 of which were collected in the hibernation season (group I) and the other 10 collected during the active period (group II). Blood, liver, brown adipose tissue (BAT) and brain samples were used to determine free radical and antioxidant levels. The results indicated a significant decrease of free radicals and increase of vitamin C, especially in serum during hibernation. In contrast, during the active period free radicals, enzymatic antioxidants as glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) and non-enzymatic antioxidants as reduce glutathione (GSH) and vitamin E increased in all studied tissues. It can be concluded that Uromastyx philbyi has a strong antioxidant defense system that protects it from the injurious effects of free radicals either at the periods of arousal or during activity periods.     

Oxygen free radicals in essential hypertension

Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, super oxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p < 0.01) in Gp IIC (243.04 ± 24.9 × 10³ counts per minute) as compared to Gp IIA (2.80 ± 1.87), Gp IIB (34.54 ± 30.24) and Gp I (0.52 ± 0.15) and SOD was reduced significantly (p < 0.05) in all EH (Gp IIA 3.9 ± 0.3 units per mg protein, Gp IIB 3.5 ± 0.3 and Gp IIC 3.12 ± 0.3) as compared to controls (4.1 ± 0.2). Similarly GSH was reduced (p < 0.05) in EH (Gp IIA 11.2 ± 1.7 mg per gm protein, Gp IIB 8.5 ± 1.1 and Gp IIC 6.6 ± 0.3) as compared to Gp I (13.5 ± 2.5). In essential hypertensives a curvilinear positive correlation was obtained between CL and both systolic (r = 0.7077, p < 0.01) and diastolic (r = 0.7965, p < 0.01) blood pressure. A significant inverse correlation (p < 0.05) was obtained between systolic and diastolic blood pressure on one hand and GSH and SOD on the other. Thus PMNLs of EH have increased emission of CL and depletion of antioxidants. The results indicate that in essential hypertension increased membrane NADPH oxidase activity is present.Abbreviations EH Essential Hypertensives - PMNLs Polymorphonuclear leucocytes - OFR Oxygen derived free radicals - Gp Group - NADPH Reduced Nicotinamide Adenine Dinucleotide Phosphate - CL Chemiluminescence - SOD Superoxide Dismutase - GSH Reduced Glutathione - SBP Systolic blood pressure - DBP Diastolic blood pressure     

Oral vitamin C and E combination modulates blood lipid peroxidation and antioxidant vitamin levels in maximal exercising basketball players

Oxidative stress occurs during maximal exercise, perhaps as a result of increased consumption of oxygen. Vitamins C and E can overcome the effects of antioxidants in exercise. We investigated the effects of supplementation with a combination of vitamin C and E (VCE) on blood lipid peroxidation (LP) and antioxidant levels following maximal training in basketball players. Blood samples were taken from 14 players (group A) and divided into two subgroups namely maximal training (group B) and maximal training plus VCE groups (group C). Group B maximally exercised for 35 days. VCE was supplemented to group C for 35 days and blood samples were taken from group B and C. Plasma and hemolyzed erythrocyte samples were obtained from the players. Erythrocyte glutathione peroxidase (GSH‐Px) activity and plasma vitamin E concentration were lower in group B than in group A, whereas plasma and erythrocyte LP levels were higher in group B than in group A. Plasma vitamin A, vitamin E, erythrocyte GSH‐Px, and reduced glutathione (GSH) values were higher in group C than in groups A and B although LP levels in plasma and erythrocytes were lower in group C than in group A and B. β‐Carotene values did not change in the three groups. In conclusion, VCE supplementation in maximal exercising basketball players may strengthen the antioxidant defense system by decreasing reactive oxygen species (ROS). Copyright © 2010 John Wiley & Sons, Ltd.     

Ascorbate-dependent recycling of the vitamin E homologue Trolox by dihydrolipoate and glutathione in murine skin homogenates

In the redox antioxidant network, dihydrolipoate can synergistically enhance the ascorbate-dependent recycling of vitamin E. Since the major endogenous thiol antioxidant in biological systems is glutathione (GSH) it was of interest to compare the effects of dihydrolipoate with GSH on ascorbate-dependent recycling of the water-soluble homologue of vitamin E, Trolox, by electron spin resonance (ESR). Trolox phenoxyl radicals were generated by a horseradish peroxidase (HRP)-hydrogen peroxide (H2O2) oxidation system. In the presence of dihydrolipoate, Trolox radicals were suppressed until both dihydrolipoate and endogenous levels of ascorbate in skin homogenates were consumed. Similar experiments made in the presence of GSH revealed that Trolox radicals reappeared immediately after ascorbate was depleted and that GSH was not able to drive the ascorbate-dependent Trolox recycling reaction. However, at higher concentrations GSH was able to increase ascorbate-mediated Trolox regeneration from the Trolox radical. ESR and spectrophotometric measurements demonstrated the ability of dihydrolipoate or GSH to react with dehydroascorbate, the two-electron oxidation product of ascorbate in this system. Dihydrolipoate regenerated greater amounts of ascorbate at a much faster rate than equivalent concentrations of GSH. Thus the marked difference between the rate and efficiency of ascorbate generation by dihydrolipoate as compared with GSH appears to account for the different kinetics by which these thiol antioxidants influence ascorbate-dependent Trolox recycling.     

Topiramate and Vitamin E Modulate the Electroencephalographic Records,Brain Microsomal and Blood Antioxidant Redox System in Pentylentetrazol-Induced Seizure of Rats

We investigated the effects of vitamin E and topiramate (TPM) administrations on pentylentetrazol (PTZ)–induced blood and brain toxicity in rats. Forty rats were randomly divided into five equal groups. The first and second groups were used for the control and PTZ groups, respectively. Fifty or 100 mg TPM were administered to rats constituting the third and fourth groups for 7 days, respectively. The TPM and vitamin E combination was given to animals in the fifth group. At the end of 7 days, all groups except the first received a single dose of PTZ. Blood and brain samples were taken at 3 hrs after PTZ administration. Lipid peroxidation levels of plasma, erythrocyte, brain cortex and brain microsomal fraction; nitric oxide levels of serum; and the number of spikes and epileptiform discharges of the EEG were increased by PTZ administration. Plasma and brain vitamin E concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and latency to first spike of the EEG were decreased by PTZ. Plasma lipid peroxidation levels in the third group and plasma and erythrocyte lipid peroxidation levels in the fifth group were decreased compared to the second group, whereas brain vitamin C, vitamin E, erythrocyte GSH-Px and reduced glutathione (GSH) values increased in the fifth group. Brain microsomal GSH levels and EEG records in the third, fourth and fifth groups were restored by the TPM and vitamin E treatment. In conclusion, TPM and vitamin E seems to have protective effects on PTZ-induced blood and brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.     

Blood plasma levels of lipoperoxides,glutathione peroxidase,beta carotene,vitamin A and E in women with habitual abortion

The plasma levels of lipoperoxides, glutathione peroxidase (GSH-Px), reduced glutathione (GSH), beta carotene, vitamin A, E, some plasma biochemical and blood haematological parameters were investigated in 40 women with habitual abortion (HA) and controls. The levels of GSH, vitamin A, E and beta carotene were significantly lower in women with HA than in controls. However, the plasma levels of lipid peroxidation, alkaline phosphatase (ALP), glucose and blood haemoglobin were significantly higher in HA than in controls. In addition, plasma levels of GSH-Px, AST, ALT, total bilirubin, total protein, albumin, sodium, potassium, calcium and number of white blood cells, red blood cells, platelet and values of packet cell volume showed no significant differences between HA and controls. According to the results of this study, we observed that the levels of lipid peroxidation were increased and plasma levels of vitamin A, E and beta carotene were decreased in HA. The decrease of those antioxidants may play a significant role in women with habitual abortion. Copyright © 1998 John Wiley & Sons, Ltd.     

Antioxidants and cataract

Abstract

The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.     

The effect of long-term enrichment of diet with selenium, vitamin E and B15 on the activity of certain enzymes in rat brain

The aim of this study was tracing of changes in the activity of glutathione peroxidase (GSHPx), glutathione transferase (GSH S-Tr), aspartate aminotransferase (AspAT) and alanine aminotransferase (A1AT) in the brain as a result of diet enrichment with antioxidants: selenium (Se), vitamin E and vitamin B15 (pangamic acid). The experiment was carried out on Wistar rats with initial body weight 150 g. Following prolonged enrichment of diet with Se (0.1 ppm of sodium selenite), vitamin E (6 mg/100 g of diet) and vitamin B15 (2.5 mg/100 g of diet) the following results were obtained. The activity of GSHPx in brain microsomes was not changed after one year of vitamin E administration when it was measured against hydrogen hydroxide and against cumene hydrochloride; vitamin E administration increased the activity of GSH S-Tr in the cytoplasmic fraction of brain cells. Diet enrichment with selenium increased after 12 and 18 months the activity of GSHPx measured against both substrates, and GSH S-Tr activity increased considerably. Presence of vitamin B15 in diet reduced GSHPx activity after one-year or longer administration, after 18 months the activity of GSH S-Tr was reduced also. No changes were noted in the activity of AspAT and A1AT.     

Antioxidants and lipid peroxidation status in the blood of patients with alopecia

The aim of this research was to determine levels in blood of vitamin E, beta-carotene, lipid peroxidation as thiobarbituric-acid reactive substances (TBARS) and reduced glutathione (GSH) and activity of glutathione peroxidase (GSH-Px) in patients with alopecia. Studies were carried out on 37 patients with alopecia and 34 healthy age-matched controls. Red blood cell (RBC) and plasma samples from healthy and patient subjects were taken. Beta-cartotene levels (P<0. 001) in plasma and levels of GSH (P>0.05) and the activity of GSH-Px (P<0.05, P<0.01) in both plasma and RBC samples were significantly lower in patients with alopecia than in controls, whereas TBARS levels in plasma (P<0.05) and RBC (P<0.001) samples were significantly higher in patients with alopecia than in controls. However, vitamin E levels in plasma did not differ statistically. Although being far from conclusive, these results provide some evidence for a potential role of increased lipid peroxidation and decreased antioxidants in alopecia.     

The use of ELISA to monitor amplified hemolysis by the combined action of osmotic stress and radiation: potential applications

A new assay has been developed to study the osmotic fragility of red blood cells (RBCs) and the involvement of oxygen-derived free radicals and other oxidant species in causing human red blood cell hemolysis. The amount of hemoglobin released into the supernatant, which is a measure of human red blood cell hemolysis, is monitored using an ELISA reader. This ELISA-based osmotic fragility test compared well with the established osmotic fragility test, with the added advantage of significantly reduced time and the requirement of only 60 mul of blood. This small amount of blood was collected fresh by finger puncture and was immediately diluted 50 times with PBS, thus eliminating the use of anticoagulants and the subsequent washings. Since exposure of RBCs to 400 Gy gamma radiation caused less than 5% hemolysis 24 h after irradiation, the RBC hemolysis induced by gamma radiation was amplified by irradiating the cell in hypotonic saline. The method was validated by examining the protective effect of Trolox, an analog of vitamin E and reduced glutathione (GSH), a well-known radioprotector, against human RBC hemolysis caused by the combined action of radiation and osmotic stress. Trolox, a known membrane stabilizer and an antioxidant, and GSH offered significant protection. This new method, which is simple and requires significantly less time and fewer RBCs, may offer the ability to study the effects of antioxidants and membrane stabilizers on human red blood cell hemolysis induced by radiation and oxidative stress and assess the osmotic fragility of erythrocytes.     

Effect of vitamin E on the degradation of hydrogen peroxide in cultured human umbilical vein endothelial cells

Vitamin E reacts with radicals such as lipid peroxyl radical (LOO*) and singlet oxygen ((1)O2), and plays a role in inhibiting lipid peroxidation in cell membranes and preventing the oxidation of low-density lipoproteins (LDL). However, only a few studies have investigated the effect of vitamin E on the degradation of hydrogen peroxide (H2O2). Therefore, we examined the effect of vitamin E on glutathione redox cycle-dependent H2O2 degradation activity in human umbilical vein endothelial cells (HUVEC). Confluent HUVEC were cultured for seven days in media containing various concentrations of vitamin E (alpha-tocopherol). The level of glutathione redox cycle-dependent H2O2 degradation activity and the intracellular glutathione level were determined. HUVEC that had been cultured in the presence of higher concentrations of vitamin E had a higher level of H2O2 degradation activity and a higher intracellular content of the reduced form of glutathione (GSH). Therefore, it is suggested that the vitamin E-induced increase in H2O2 degradation activity in HUVEC results from an increase in intracellular GSH level.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

Glycine Provokes Lipid Oxidative Damage and Reduces the Antioxidant Defenses in Brain Cortex of Young Rats

Patients affected by nonketotic hyperglycinemia (NKH) usually present severe neurological symptoms and suffer from acute episodes of intractable seizures with leukoencephalopathy. Although excitotoxicity seems to be involved in the brain damage of NKH, the mechanisms underlying the neuropathology of this disease are not fully established. The objective of the present study was to investigate the in vitro effects of glycine (GLY), that accumulate at high concentrations in the brain of patients affected by this disorder, on important parameters of oxidative stress, such as lipid peroxidation (thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence) and the most important non-enzymatic antioxidant defense reduced glutathione (GSH) in cerebral cortex from 30-day-old rats. GLY significantly increased TBA-RS and chemiluminescence values, indicating that this metabolite provokes lipid oxidative damage. Furthermore, the addition of high doses of the antioxidants melatonin, trolox (soluble vitamin E) and GSH fully prevented GLY-induced increase of lipid peroxidation, indicating that free radicals were involved in this effect. GLY also decreased GSH brain concentrations, which was totally blocked by melatonin treatment. Finally, GLY significantly reduced sulfhydryl group content from a commercial GSH solution, but did not oxidize reduced cytochrome C. Our data indicate that oxidative stress elicited in vitro by GLY may possibly contribute at least in part to the pathophysiology of the neurological dysfunction in NKH.     

Vitamin C and vitamin E restore the resistance of GSH-depleted lens cells to H2O2

A decline in reduced glutathione (GSH) levels is associated with aging and many age-related diseases. The objective of this study was to determine whether other antioxidants can compensate for GSH depletion in protection against oxidative insults. Rabbit lens epithelial cells were depleted of > 75% of intracellular GSH by 25-200 microM buthionine sulfoximine (BSO). Depletion of GSH by BSO alone had little direct effect on cell viability, but resulted in an approximately 30-fold increase in susceptibility to H(2)O(2)-induced cell death. Experimentally enhanced levels of nonprotein sulfhydryls other than GSH (i.e., N-acetylcysteine) did not protect GSH-depleted cells from H(2)O(2)-induced cell death. In contrast, pretreatment of cells with vitamin C (25-50 microM) or vitamin E (5-40 microM), restored the resistance of GSH-depleted cells to H(2)O(2). However, concentrations of vitamin C > 400 microM and vitamin E > 80 microM enhanced the toxic effect of H(2)O(2). Although levels of GSH actually decreased by 10-20% in cells supplemented with vitamin C or vitamin E, the protective effects of vitamin C and vitamin E on BSO-treated cells were associated with significant ( approximately 70%) decreases in oxidized glutathione (GSSG) and concomitant restoration of the cellular redox status (as indicated by GSH:GSSG ratio) to levels detected in cells not treated with BSO. These results demonstrate a role for vitamin C and vitamin E in maintaining glutathione in its reduced form. The ability of vitamin C and vitamin E in compensations for GSH depletion to protect against H(2)O(2)-induced cell death suggests that GSH, vitamin C, and vitamin E have common targets in their actions against oxidative damage, and supports the preventive or therapeutic use of vitamin C and E to combat age- and pathology-associated declines in GSH. Moreover, levels of these nutrients must be optimized to achieve the maximal benefit.     

Significance of melatonin in antioxidative defense system: reactions and products

Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H(2)O(2)), hydroxyl radical (HO(.)), nitric oxide (NO(.)), peroxynitrite anion (ONOO(-)), hypochlorous acid (HOCl), singlet oxygen ((1)O(2)), superoxide anion (O(2)(-).) and peroxyl radical (LOO(.)), although the validity of its ability to scavenge O(2)(-). and LOO(.) is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO. Also, its secondary and tertiary metabolites, for example, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.     

Effects of photodynamic treatment on biological antioxidant systems in rats

Effects of photodynamic treatments on inherent antioxidant metabolites and cellular defence enzymes have been investigated in rats. Wistar rats were grouped into untreated controls, light controls, hematoporphyrin derivative (Hpd) (treated with 5 and 10 mg Hpd/kg body weight and kept in dark) and sets treated with both Hpd and red light (dose 172 and 344 j/m2 ). After 2, 24, 48 and 72 hr of Hpd injection the rats sacrificed, livers quickly excised to analyze Hpd uptake, activities of enzymes like catalase, GSH-Px and antioxidants like GSH, vitamin A, vitamin E and vitamin C. The results showed that the loss of Hpd from liver as a function of post- injection time was non- linear. An increased generation of lipid radicals was observed in the groups treated with 5 mg Hpd and higher dose of light and in groups treated with 10 mg Hpd at both the doses of light. Combination of light and Hpd reduced hepatic GSH content with a concomitant reduction in GSH-Px. At higher doses of Hpd and light, there was a significant reduction in hepatic vitamin A levels. Combination of Hpd and light in all doses reduced vitamin E content in liver. The decreased biological antioxidant contents and GSH-Px may be attributed to their utilization for the scavenging of free radicals generated by Hpd and light in tissues. However, no change in catalase activity and vitamin C content in liver was noted in experimental rats. The results suggest that exposure to higher doses of Hpd with light alters oxidant stress system and TBARS content in rat.     

Systemic oxidative stress in children and teenagers with Down syndrome

Aims

The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome.

Main methods

The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n = 20) compared to healthy controls (n = 18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically.

Key Findings

Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls.

Significance

The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.     

Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes

Protective effect of various antioxidants, trolox (water soluble analogue of vitamin E), quercetin (bioflavonoid) and glutathione reduced (GSH), was studied following sulphur mustard (SM) intoxication. SM, a blistering agent was administered to Swiss albino female mice through inhalation (1 LC50=42.3 mg/m3 for 1 h duration; 14 days observation for mortality) and percutaneous (1 LD50=154.7 mg/kg; 7 days observation for mortality) routes. The antioxidants were administered three times at the dose of trolox, 500 microg/kg; quercetin, 5 mg/kg and GSH, 400 mg/kg body weight by intraperitoneal injection, one immediately following SM exposure, then once each day for 2 days after SM treatment. The effect of antioxidants on survival, markers of oxidative damage and purine metabolites was investigated. Survival study animals were observed for 14 days. Oxidative markers (in blood, liver and lung) and purine metabolites (in blood and urine) were investigated 72 h after SM treatment. Survival time increased significantly following trolox and quercetin treatments through the inhalation route. Significant decrease in GSH and increase in the level of malondialdehyde (MDA) indicated oxidative damage to liver and lung tissues following SM inhalation and percutaneous exposure. Blood and urinary uric acid, end product of purine metabolism showed an increased following both routes of exposures. The antioxidants, trolox and quercetin protected the liver and lung tissues from oxidative damage caused by SM exposure through inhalation and percutaneous routes. This study showed that antioxidants could enhance survival time, protect liver and lung from oxidative damage and reduce accumulation of purine metabolites in blood following SM intoxication.     

Ascorbic acid supplementation causes faster restoration of reduced glutathione content in the regression of alcohol-induced hepatotoxicity in male guinea pigs

Abstract

Alcoholic liver disease is caused mainly by free radicals. Ascorbic acid (AA) and glutathione (GSH) are the major water-soluble antioxidants in the liver. The impact of AA supplementation on GSH, AA and activities of GSH-dependent enzymes in alcoholic guinea pigs was studied and was compared with alcohol abstention. Guinea pigs were administered ethanol at a dose of 4 g/kg body weight (b.wt)/day for 90 days. After 90 days, alcohol administration was stopped and one-half of the ethanol-treated animals were supplemented with AA (25 mg/100 g b.wt) for 30 days and the other half was maintained as the abstention group. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase in the serum of the ethanol group. In addition, a significant decrease in the GSH content, activities of GSH peroxidase, GSH reductase, and increased activity of GSH-S-transferase were observed in the liver of the ethanol group. Histopathological analysis and triglycerides content in the liver of the ethanol group showed induction of steatosis. But AA supplementation and abstention altered the changes caused by ethanol. However, maximum protective effect was observed in the AA-supplemented group indicating the ameliorative effect of AA in the liver.     

Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetes

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and metformin on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin-nicotinamide induced type 2 diabeteic model was investigated. Succinic acid monoethyl ester was administered intraperitonially for 30 days to control and diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of EMS was compared with metformin, a reference drug. The levels of glucose, glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased significantly whereas the level of insulin and hemoglobin, as well as antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in EMS and metformin treated diabetic rats. The present study indicates that the EMS possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.