Antioxidant vitamin levels and glutathione peroxidase activity during ischemia/reperfusion in myocardial infarction

The consequences of increased oxidative stress, measured as the level of malondialdehyde (MDA) during ischemia/reperfusion, were studied in 48 patients in the acute phase of myocardial infarction (AMI) and a control group (21 blood donors). The serum levels of alpha-tocopherol and beta-carotene were followed. Immediately after the treatment onset the level of alpha-tocopherol started to decrease, reaching a plateau after 24 h. The consumption of beta-carotene was delayed by 90 min. Steady decline was detected during the whole time interval studied (48 h). Glutathione peroxidase (GPx) activity, as a representative of antioxidant enzymes, was estimated in whole blood. The influx of oxygenated blood was accompanied by a stimulation of GPx activity, which reached its maximum at the time of completed reperfusion. When comparing the AMI patients with the control group, the levels of MDA were found significantly increased, which indicates that oxidative stress is already increased during ischemia. Lower antioxidant levels found in the patients might either already be the result of vitamin consumption during ischemia or be a manifestation of their susceptibility to AMI. Monitored consumption of alpha-tocopherol and beta-carotene during reperfusion indicated that in the case of patients, whose level of antioxidant vitamins is below the threshold limit, a further substantial decrease of antioxidant vitamins during reperfusion could enhance the oxidative damage of the myocardium.     

Sensitization by docosahexaenoic acid (DHA) of breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response

Docosahexaenoic acid (DHA, a lipid of marine origin) has been found to enhance the activity of several anticancer drugs through an oxidative mechanism. To examine the relation between chemosensitization by DHA and tumor cells antioxidant status, we used two breast cancer cell lines: MDA-MB-231, in which DHA increases sensitivity to doxorubicin, and MCF-7, which does not respond to DHA. Under these conditions, reactive oxygen species (ROS) level increased on anthracycline treatment only in MDA-MB-231. This was concomitant with a decreased cytosolic glutathione peroxidase (GPx1) activity, a crucial enzyme for protection against hydrogen and lipid peroxides, while major antioxidant enzyme activities increased in both cell lines in response to ROS. GPx-decreased activity was accompanied by an accumulation of glutathione, the GPx cosubstrate, and resulted from a decreased amount of GPx protein. In rat mammary tumors, when a DHA dietary supplementation led to an increased tumor sensitivity to anthracyclines, GPx1 activity was similarly decreased. Furthermore, vitamin E abolished both DHA effects on chemotherapy efficacy enhancement and on GPx1 inhibition. Thus, loss of GPx response to an oxidative stress in transformed cells may account for the ability of peroxidizable targets such as DHA to enhance tumor sensitivity to ROS-generating anticancer drugs.     

Effects of Bacillus thuringiensis toxin on hepatic lipid peroxidation and free-radical scavengers in rats given alpha-tocopherol or acetylsalicylate

The effect of Dipel (D), a Bacillus thuringiensis-based bioinsecticide, on hepatic antioxidant enzyme activities and lipid peroxidation in rat liver was investigated. Administration of D in a dose of 1 mg/100 g body mass for 4 successive days increased the activities of glutathione peroxidase (GPx), glutathione reductase (GR) and the level of malondialdehyde (MDA) in rat hepatocytes. The activity of superoxide dismutase (SOD) and glutathione (GSH) level were decreased. Administration of D in rats pretreated with alpha-tocopherol (alphaT) or acetylsalicylic acid (ASA) decreased the activities of GPx, GR and MDA levels, while the GSH level was increased compared with rats treated with D alone. The SOD activity was increased in rats pretreated with alphaT before D, but decreased on pretreatment with ASA, compared with rats treated with D alone. The results indicated that D induced oxidative stress in rat liver that has been protected by prior administration of alphaT or ASA.     

Effects of low selenium diets on antioxidant status and MPTP toxicity in mice

To investigate the role of chronic oxidative stress in MPTP neurotoxicity, C57BL mice were maintained 6–8 weeks on diets deficient in nutrients essential to cellular antioxidant defenses, selenium (Se) and alpha-tocopherol (vit E), and the effects on tissue antioxidant status and MPTP toxicity were evaluated relative to controls on supplemented diets. Activities of the major antioxidant enzymes, glutathione peroxidase (GPx), catalase, and superoxide dismutase, and levels of malondialdehyde as a marker for oxidative stress, were measured in brain, lung, liver and blood. Caudate depletion of dopamine and its metabolites served as a measure of MPTP neurotoxicity. For mice on the Se deficient diet, levels of the selenoenzyme GPx decreased from 50% in brain to 90% in blood. No compensatory changes in the activities of the other antioxidant enzymes were observed and addition of vit E to the diet did not alter antioxidant enzyme activities or malondialdehyde levels. In animals not treated with MPTP, the Se deficient diet significantly increased malondialdehyde only in liver. No protective effect of the antioxidant supplements against caudate depletion of dopamine and its metabolites was observed. However, malondialdehyde levels were increased in the brains of MPTP treated mice on the low Se diets, suggesting the possibility of secondary oxidative damage to tissues accompanying the destruction of substantia nigra neurons by MPTP.     

Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

The effects of MDMA administration on oxidative stress markers in rat eye and hippocampus, and the neuroprotective effects of the antioxidant 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6) have been studied. MDMA effects on liver were used for comparison with those in eye and hippocampus and to test CR-6 protective effects. Another goal was to test for apoptosis in retinal cells, as it is known that happens in liver and brain. After 1 week of ecstasy administration, malondialdehyde (MDA) concentration increased, glutathione peroxidase (GPx) activity and glutathione (GSH) content decreased in liver, as previously described. MDA concentration increased and GPx activity decreased in hippocampus; whereas no change was observed in GSH concentration. MDMA decreased ocular GSH concentration and GPx activity; no change was observed in MDA concentration. The number of TUNEL-positive nuclei increased significantly in rat retinas after 1 week of MDMA administration. CR-6 normalized the modifications in liver, hippocampus and retina mentioned above.     

Morphological alterations and induction of oxidative stress in glial cells caused by the branched-chain alpha-keto acids accumulating in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited neurometabolic disorder biochemically characterized by the accumulation of the branched-chain alpha-keto acids (BCKA) alpha-ketoisocaproic (KIC), alpha-keto-beta-methylvaleric (KMV) and alpha-ketoisovaleric (KIV) and their respective branched-chain alpha-amino acids in body fluids and tissues. Affected MSUD patients have predominantly neurological features, including cerebral edema and atrophy whose pathophysiology is not well established. In the present study we investigated the effects of KIC, KMV and KIV on cell morphology, cytoskeleton reorganization, actin immunocontent and on various parameters of oxidative stress, namely total antioxidant reactivity (TAR), glutathione (GSH) and nitric oxide concentrations, and on the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in C6 glioma cells. We initially observed that C6 cultivated cells exposed for 3 h to the BCKA (1 and 10 mM) changed their usual rounded morphology to a fusiform or process-bearing cell appearance, while 24 h exposure to these organic acids elicited massive cell death. Rhodamine-labelled phalloidin analysis revealed that these organic acids induced reorganization of the actin cytoskeleton with no modifications on total actin content. It was also observed that 3h cell exposure to low doses of all BCKA (1 mM) resulted in a marked reduction of the non-enzymatic antioxidant defenses, as determined by TAR and GSH measurements. In addition, KIC provoked a reduced activity of SOD and GPx, whereas KMV caused a diminution of SOD activity. In contrast, CAT activity was not modified by the metabolites. Furthermore, nitric oxide production was significantly increased by all BCKA. Finally, we observed that the morphological features caused by BCKA on C6 cells were prevented by the use of the antioxidants GSH (1.0 mM), alpha-tocopherol (trolox; 10 microM) and Nomega-nitro-L-arginine methyl ester (L-NAME; 500 microM). These results strongly indicate that oxidative stress might be involved in the cell morphological alterations and death, as well as in the cytoskeletal reorganization elicited by the BCKA. It is presumed that these findings are possibly implicated in the neuropathological features observed in patients affected by MSUD.     

Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal caco-2 cells

Oxidative stress has been linked to the development of various chronic diseases. Vegetables and fruits, which contain polyphenols, were shown to have protective effects. (-)-Epigallocatechin-3-gallate (EGCG), a polyphenol abundant in tea, has been shown to have antioxidant activities in cell-free conditions and this study focused on the effect of cellular EGCG. Using an intestinal cell model to examine the oxidative stress induced by hydroxyl radicals, we report here that physiological concentrations (0.1-1 microM) of EGCG have dose- and incubation duration-dependent cell-associated lipid antioxidant activity (measuring malondialdehyde production). Vitamin E and vitamin C at 10-40 microM also showed cell-associated lipid antioxidant activities under shorter incubation durations. When EGCG was included in the incubation with vitamin E or C, more antioxidant activities were consistently observed than when vitamins were added alone. Catechin (widely present in fruits and vegetables) at 1 microM also significantly increased the antioxidant activity of vitamins E and C. Previous studies examining cell-associated activity of EGCG mainly focused on the 10-100 microM concentration range. Our results suggest that although the physiological level (0.1-1 microM) of dietary catechins is much lower than that of vitamins, they further contribute to the total antioxidant capacity even in the presence of vitamins.     

Response of the antioxidant defense system to tert-butyl hydroperoxide and hydrogen peroxide in a human hepatoma cell line (HepG2)

The aim of this work was to investigate the response of the antioxidant defense system to two oxidative stressors, hydrogen peroxide and tert-butyl hydroperoxide, in HepG2 cells in culture. The parameters evaluated included enzyme activity and gene expression of superoxide dismutase, catalase, glutathione peroxidase, and activity of glutathione reductase. Besides, markers of the cell damage and oxidative stress evoked by the stressors such as cell viability, intracellular reactive oxygen species generation, malondialdehyde levels, and reduced glutathione concentration were evaluated. Both stressors, hydrogen peroxide and tert-butyl hydroperoxide, enhanced cell damage and reactive oxygen species generation at doses above 50 microM. The concentration of reduced glutathione decreased, and levels of malondialdehyde and activity of the antioxidant enzymes consistently increased only when HepG2 cells were treated with tert-butyl hydroperoxide but not when hydrogen peroxide was used. A slight increase in the gene expression of Cu/Zn superoxide dismutase and catalase with 500 microM tert-butyl hydroperoxide and of catalase with 200 microM hydrogen peroxide was observed. The response of the components of the antioxidant defense system evaluated in this study indicates that tert-butyl hydroperoxide evokes a consistent cellular stress in HepG2.     

Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity

A major fraction of the essential trace element selenium circulating in human blood plasma is present as selenoprotein P (SeP). As SeP associates with endothelial membranes, the participation of SeP in selenium-mediated protection against oxidative damage was investigated, using the human endothelial cell line Ea.hy926 as a model system. Hepatocyte-derived SeP prevented tert-butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a similar manner as did sodium selenite, counteracting a t-BHP-induced loss of cellular membrane integrity. Protection was detected after at least 10 h of SeP supplementation and it peaked at 24 h. SeP time-dependently stimulated the expression of cytosolic glutathione peroxidase (cGPx) and increased the enzymatic activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR). The cGPx inhibitor mercaptosuccinate as well as the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while the TR inhibitors cisplatin and auranofin had no effect. The presented data suggest that selenium supplementation by SeP prevents oxidative damage of human endothelial cells by restoring expression and enzymatic activity of GPx.     

Dietary docosahexaenoic acid enhances ferric nitrilotriacetate-induced oxidative damage in mice but not when additional alpha-tocopherol is supplemented

Weaning mice were fed a diet supplemented with beef tallow (BT) or BT plus docosahexaenoic acid (DHA) containing 100 mg alpha-tocopherol/kg (alpha-Toc100) or 500 mg alpha-tocopherol/kg (alpha-Toc500) for 4 wk to modify membrane fatty acid unsaturation, and then were administered ferric nitrilotriacetate (Fe-NTA). The mortality caused by Fe-NTA was higher in the group fed the DHA (alpha-Toc100) diet than in the BT diet groups but the DHA (alpha-Toc500) diet suppressed this increase. Serum and kidney alpha-tocopherol contents were slightly influenced by the dietary fatty acids but not significantly. These results indicate that the increased unsaturation of tissue lipids enhances oxidative damage induced by Fe-NTA in mice fed DHA (alpha-Toc100) but not when additional alpha-tocopherol is supplemented. The apparent discrepancy between the observed enhancement by dietary DHA of oxidative damage and the beneficial effects of dietary DHA on the so-called free radical diseases is discussed in terms of strong bolus oxidative stress and moderate chronic oxidative stress.     

Lipid peroxidation, antioxidant status and survival in institutionalised elderly: a five-year longitudinal study

Oxidative stress has been related to ageing and risk of death. To determine whether oxidative status was associated with all-cause risk of death we carried out a prospective study in 154 non-smoking Spanish elderly without major illness. Baseline glutathione peroxidase (GPx) and superoxide dismutase (SOD) were analysed in plasma and erythrocytes. alpha-tocopherol, beta-carotene, lycopene and retinol were determined in serum samples and malondialdehyde (MDA), as a lipid peroxidation marker, in plasma. Mean survival time was 4.3 years. A total of 31 death cases (20.1%) occurred during the follow-up. Plasma-MDA predicted mortality independently of all other variables, while erythrocyte-SOD (e-SOD), beta-carotene and alpha-tocopherol were positively associated with survival. alpha-tocopherol and MDA were revealed as independent predictors in a joint survival model, being the group with low MDA and high alpha-tocopherol that with the lowest mortality. In conclusion, a higher risk of death was associated with increased lipid peroxidation and lower antioxidant defenses.     

CR-6 protects glutathione peroxidase activity in experimental diabetes

Antioxidants can be useful as a supportive therapy in diabetes, and we try to elucidate some of the mechanisms by which these compounds are able to protect from diabetic complications. For this purpose we have assayed, in vitro and in vivo, the ability of CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran), an antioxidant able to scavenge nitrogen reactive species, to protect glutathione peroxidase (GPx) activity. Glucose, in vitro, inhibited GPx activity in a concentration-dependent manner; CR-6 was able to protect GPx activity from glucose-induced inactivation. Alloxan-induced experimental diabetes in mice promoted oxidative stress in the retina and hippocampus, after 3 weeks of hyperglycemia. CR-6 administration prevented not only the alterations of oxidative stress markers (tissue GSH and malondialdehyde (MDA) concentration and GPx activity) but also the impairment of retinal function (as assessed by the modifications in electroretinogram b-wave amplitude). The findings herein confirm the role of nitrogen reactive species in diabetes; therefore, antioxidants effectively quenching these species, such as CR-6, should be considered for the adjuvant treatment of diabetes.     

Mitochondrial GPx1 decreases induced but not basal oxidative damage to mtDNA in T47D cells

The production of oxyradicals by mitochondria (mt) is a source of oxidative damage to mtDNA such as 8-oxo-dG lesions that may lead to mutations and mitochondrial dysfunction. The potential protection of mtDNA by glutathione peroxidase-1 (GPx1) was investigated in GPx1-proficient (GPx-2) and GPx1-deficient (Hygro-3) human breast T47D cell transfectants. GPx activity and GPx1-like antigen concentration in mitochondria were respectively at least 100-fold and 20- to 25-fold higher in GPx2 than Hygro-3 cells. In spite of this large difference in peroxide-scavenging capacity, the basal 8-oxo-dG frequency in mtDNA, assessed by carefully controlled postlabeling assay, was strikingly similar in both cell lines. In contrast, in response to menadione-mediated oxidative stress, induction of 8-oxo-dG and DNA strand breaks was much lower in the GPx1-proficient mitochondria (e.g., +14% 8-oxo-dG versus +54% in Hygro-3 after 1-h exposure to 25 microM menadione, P < 0.05). Our data indicate that the mitochondrial glutathione/GPx1 system protected mtDNA against damage induced by oxidative stress, but did not prevent basal oxidative damage to mtDNA, which, surprisingly, appeared independent of GPx1 status in the T47D model.     

Tri-iodo thyronine regulates antioxidant enzyme activities in different cell fractions through a mechanism sensitive to actinomycin D in a teleost, Anabas testudineus (Bloch)

The present study evaluated the effects of hyperthyroid state on lipid peroxidation and antioxidant enzymes in the crude (CF), post nuclear (PNF) and mitochondrial fractions (MF) of the fish liver. The in vivo injection of T3 (200ng) did not change the lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes (CD), while actinomycin D (10microg), a potent mRNA inhibitor when administered with T3 increased them. The antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) had an increased activity in CF and MF of hyperthyroid group to compete the increased oxidative stress, but actinomycin D partially inhibited the T3-induced activity. SOD and CAT activities in PNF of hyperthyroid group had no change, the glutathione concentration varied depending on the GPx and GR activity. Hyperthyroidism decreased the protein content, while simultaneous administration of actinomycin D inhibited the T3 action of elevating the protein content. The results suggest that the antioxidant defense status in A. testudineus is modulated by thyroid hormone, through an action sensitive to actinomycin D.     

Cytoprotective properties of alpha-tocopherol are related to gene regulation in cultured D-galactosamine-treated human hepatocytes

Vitamin E (alpha-tocopherol) has demonstrated antioxidant activity and gene-regulatory properties. d-Galactosamine (D-GalN)-induced cell death is mediated by nitric oxide in hepatocytes, and it is associated with hepatic steatosis. The beneficial properties of alpha-tocopherol and their relation to oxidative stress and gene regulation were assessed in D-GalN-induced cell death. Hepatocytes were isolated from human liver resections by a collagenase perfusion technique. alpha-Tocopherol (50 microM) was administered at the advanced stages (10 h) of D-GalN-induced cell death in cultured hepatocytes. Cell death, oxidative stress, alpha-tocopherol metabolism, and NF-kappaB-, pregnane X receptor (PXR)-, and peroxisome proliferator-activated receptor (PPAR-alpha)-associated gene regulation were estimated in the hepatocytes. D-GalN increased cell death and alpha-tocopherol metabolism. alpha-Tocopherol exerted a moderate beneficial effect against apoptosis and necrosis induced by D-GalN. Induction (rifampicin) or inhibition (ketoconazole) of alpha-tocopherol metabolism and overexpression of PXR showed that the increase in PXR-related CYP3A4 expression caused by alpha-tocopherol enhanced cell death in hepatocytes. Nevertheless, the reduction in NF-kappaB activation and inducible nitric oxide synthase expression and the enhancement of PPAR-alpha and carnitine palmitoyl transferase gene expression by alpha-tocopherol may be relevant for cell survival. In conclusion, the cytoprotective properties of alpha-tocopherol are mostly related to gene regulation rather than to antioxidant activity in toxin-induced cell death in hepatocytes.     

2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase

Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK) by mitochondria-derived reactive oxygen species (ROS) is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC) treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG). Treatment of BAEC with 2-DG (5 mM) for 24 hours or with low concentrations of H(2)O(2) (100 μM) induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine) or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress.     

The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity

Usually, all newborns demonstrate high serum unconjugated bilirubin (UCB) level. UCB may induce adverse effects in the central nervous system. We aimed to evaluate the cytotoxic effects of UCB and the protective effects of docosahexaenoic acid (DHA) on astrocyte cell cultures. The viability of astrocyte cells decreased after UCB treatment in a dose-dependent manner. Pre-incubation of DHA prevents the cells from UCB-mediated neurotoxicity. Our results shown that UCB leads to inhibition of antioxidant enzymes superoxide dismutase (SOD), catalase and GPx activity and induction of apoptosis. But only 4-h pretreatment of DHA can suppress of UCB-mediated inhibition of antioxidant enzymes SOD, catalase and GPx activity and induction of apoptosis in astrocytes. Our results strongly indicated that DHA has a protective effect on UCB-mediated neurotoxicity through inhibition apoptosis and antioxidant enzymes activity of SOD, CAT and GPx in rat primer astrocyte cell line     

Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity

A major fraction of the essential trace element selenium circulating in human blood plasma is present as selenoprotein P (SeP). As SeP associates with endothelial membranes, the participation of SeP in selenium-mediated protection against oxidative damage was investigated, using the human endothelial cell line Ea.hy926 as a model system. Hepatocyte-derived SeP prevented tert-butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a similar manner as did sodium selenite, counteracting a t-BHP-induced loss of cellular membrane integrity. Protection was detected after at least 10 h of SeP supplementation and it peaked at 24 h. SeP time-dependently stimulated the expression of cytosolic glutathione peroxidase (cGPx) and increased the enzymatic activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR). The cGPx inhibitor mercaptosuccinate as well as the γ-glutamylcysteine synthetase inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while the TR inhibitors cisplatin and auranofin had no effect. The presented data suggest that selenium supplementation by SeP prevents oxidative damage of human endothelial cells by restoring expression and enzymatic activity of GPx.     

Glutathione peroxidases and redox-regulated transcription factors

Analysis of the selenoproteome identified five glutathione peroxidases (GPxs) in mammals: cytosolic GPx (cGPx, GPx1), phospholipid hydroperoxide GPx (PHGPX, GPx4), plasma GPx (pGPX, GPx3), gastrointestinal GPx (GI-GPx, GPx2) and, in humans, GPx6, which is restricted to the olfactory system. GPxs reduce hydroperoxides to the corresponding alcohols by means of glutathione (GSH). They have long been considered to only act as antioxidant enzymes. Increasing evidence, however, suggests that nature has not created redundant GPxs just to detoxify hydroperoxides. cGPx clearly acts as an antioxidant, as convincingly demonstrated in GPx1-knockout mice. PHGPx specifically interferes with NF-kappaB activation by interleukin-1, reduces leukotriene and prostanoid biosynthesis, prevents COX-2 expression, and is indispensable for sperm maturation and embryogenesis. GI-GPx, which is not exclusively expressed in the gastrointestinal system, is upregulated in colon and skin cancers and in certain cultured cancer cells. GI-GPx is a target for Nrf2, and thus is part of the adaptive response by itself, while PHGPx might prevent cancer by interfering with inflammatory pathways. In conclusion, cGPx, PHGPx and GI-GPx have distinct roles, particularly in cellular defence mechanisms. Redox sensing and redox regulation of metabolic events have become attractive paradigms to unravel the specific and in part still enigmatic roles of GPxs.     

Effects of cadmium exposure on lipid peroxidation and the antioxidant system in fourth-instar larvae of Propsilocerus akamusi (Diptera: Chironomidae) under laboratory conditions

Enzymatic antioxidants such as selenium-dependent glutathione peroxidase (GPx), glutathione transferase (GST), glutathione reductase (GR), and superoxide dismutases (SOD), as well as the concentration of hydrogen peroxide (H2O2) and malondialdehyde (MDA, an indicator of lipid peroxidation) were determined to identify which antioxidant enzymes participate in the efficient scavenging of ROS generated upon exposure to high doses of Cd2+ in fourth-instar Propsilocerus akamusi (Tokuna) (Diptera: Chironomidae) larvae after 72-h exposure. A significant increase in MDA levels and a change in GR and GPx activities in the Cd(2+)-treated P. akamusi were observed. The MDA in 25.0 and 50.0 mmol/liter treatments was significantly higher than that of the control dose after 72 h exposure. GPx activity was significantly induced by Cd2+ exposure only in the 50.0-mmol/liter treatment with a 0.59-fold increase in the control. All doses of Cd2+ significantly suppressed GR activity compared with the findings for the control dose, with an inhibited rate up to 0.55-fold in the 25.0 mmol/liter Cd2+ treatment. SOD and GST activities were not altered. The results indicate that Cd2+ can induce oxidative stress as indicated by the changes in lipid peroxidation and antioxidant status. For P. akamusi, an increase in the dose that the threshold needed for defense (namely, MDA level and GPx activity) activation was achieved. From this, organisms can be hypothesized to enable cells to avoid oxidant stress up to a certain extent where damage is again measurable (higher Cd2+ concentration).