The endothelium-derived hyperpolarizing factor, H2O2, promotes metal-ion efflux in aortic endothelial cells: elemental mapping by a hard X-ray microprobe

Hydrogen peroxide (H(2)O(2)) is a physiologic oxidant implicated in vascular cell signaling, although little is known about the biochemical consequences of its reaction with endothelial cells. Submicrometer-resolution hard X-ray elemental mapping of cultured porcine aortic endothelial cells (PAEC) has provided data on the global changes for intracellular elemental density within PAEC and indicates an efflux of metal ions and phosphorus from the cytoplasm after H(2)O(2) treatment. The synchrotron-radiation-induced X-ray emission experiments (SRIXE) show that H(2)O(2)-treated cells are irregularly shaped and exhibit blebbing indicative of increased permeability due to the damaged membrane. The SRIXE results suggest that H(2)O(2)-induced damage is largely restricted to the cell membrane as judged by the changes to membrane and cytoplasmic components rather than the cell nucleus. The SRIXE data also provide a mechanism for cell detoxification as the metal-ion efflux resulting from the initial H(2)O(2)-mediated changes to cell membrane potentially limits intracellular metal-mediated redox processes through Fenton-like chemistry. They may also explain the increased levels of these ions in atherosclerotic plaques, regardless of whether they are involved in plaque formation. Finally, the SRIXE data support the notion that cultured endothelial cells exposed to H(2)O(2) respond with enhanced cellular metal-ion efflux into the extracellular space.     

Selenium uptake and its influence on the antioxidative system of white clover as affected by lime and phosphorus fertilization

Selenium (Se) is regarded as an antioxidant in animal and human nutrition, but its biological role in plants needs to be clarified. Plants vary considerably in their ability to tolerate Se, and their biochemical response to Se may be affected by liming or P fertilization. Two greenhouse experiments were conducted with white clover (Trifolium repens L.) to evaluate Se accumulation, tolerance, and the antioxidant response at increasing selenite supply levels (from 0 to 60 g Se ha⁻¹) and the effect of lime and P on both the Se uptake and the antioxidant activity of plants treated with 0, 20 and 40 g Se ha⁻¹. Selenium concentration in plant tissues was increased by Se applications, and plant growth was reduced at Se supply levels above 20 g ha⁻¹. At shoot concentration up to 200 μg kg⁻¹ DW, Se promoted antioxidant ability by increasing the free radical scavenging activity and by inhibiting lipid peroxidation (TBARS), whereas above this level TBARS accumulation increased. Significant changes in the activities of peroxidase (POD) and ascorbate peroxidase (APX) enzymes were also observed as a consequence of the increase in shoot Se concentration. The application of lime and P improved the plant nutrition, which increased the dry matter yield and enhanced the plant’s antioxidative system. Under different combinations of soil acidity and P fertilization a differential uptake of Se by the plant occurred. These factors appear to be responsible for beneficial or detrimental effects of Se in terms of lipid peroxidation of biological membranes and the activation of POD and APX in white clover.     

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3(2H)‐one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti‐inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free‐Ca²⁺ concentration ([Ca²⁺]_c), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen‐activated protein kinases were analyzed. Our results show that ebselen evoked a concentration‐dependent increase in [Ca²⁺]_c. The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin‐evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X‐box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen‐activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells.     

Hard X-ray microprobe studies of chromium(VI)-treated V79 Chinese hamster lung cells: intracellular mapping of the biotransformation products of a chromium carcinogen

The uptake of carcinogenic and mutagenic Cr compounds and the intracellular distribution of their biotransformation products in V79 Chinese hamster lung cells were studied by synchrotron-radiation-induced X-ray emission (SRIXE). SRIXE analysis was performed on whole cells that had been treated with either Cr(III) or Cr(V) 1,10-phenanthroline complexes, or Cr(VI). The high spatial resolution (0.3 microm) and elemental sensitivity (~10(-15) g Cr/cell) of the technique provided detailed maps of Cr and other cellular elements in thin sections prepared from Cr(VI)-treated cells. The Cr carcinogen concentrated in P-rich regions corresponding to the nucleus, as well as other areas of the cell that are likely to correspond to organelles. This is the first study that has enabled the determination of the localization of the biotransformation products of Cr(VI) carcinogens in a target lung cell.     

Effect of selenium compounds on the damage induced by oxysterol on rat arterial walls

Wistar rats were fed Se-deficient (0.017±0.002 mg Se/kg) and Seadequate (0.32±0.045 Se mg/kg) diets for 12 mo and then were given 5 mg/kg of cholestane-3β,tα,6β-triol (3-triol), intravenously. Se compounds (Na₂SeO₃ and ebselen) were supplemented in different doses and times to the Se-deficient rats. Twenty-four hours after 3-triol infusion, the changes in ultrastructures of rat aorta were examined by scanning electron micrography (SEM) and transmission electron micrography (TEM). SEM examinations showed that 3-triol induced diffused injuries on arterial endothelial urfaces of long-term Se-deficient rat, and a large number of holes or craterlike defects were observed. TEM examinations further showed that 3-triol induced swelling, necrosis, and shedding of endothelial cells, which resulted in the destruction of endothelial integrity. Mean-while, smooth muscle cells proliferated and migrated toward intimae; the breakage of internal elastic lamina benefited the migration of smooth muscle cells. Supplemented with Na₂SeO₃ (40 μg/kg, 10 d per continuum) and ebselen (20 mg/kg), respectively, exhibited significant protection from damages induced by 3-triol. It seems that protecting mechanisms were different between Na₂SeO₃ and ebselen. The present investigation gave visual evidence that both injuries induced by cholesterol oxides and the Se nutritional status contributed to the development of atherosclerosis.     

Probing Intracellular Element Concentration Changes during Neutrophil Extracellular Trap Formation Using Synchrotron Radiation Based X-Ray Fluorescence

High pressure frozen (HPF), cryo-substituted microtome sections of 2 μm thickness containing human neutrophils (white blood cells) were analyzed using synchrotron radiation based X-ray fluorescence (SR nano-XRF) at a spatial resolution of 50 nm. Besides neutrophils from a control culture, we also analyzed neutrophils stimulated for 1–2 h with phorbol myristate acetate (PMA), a substance inducing the formation of so-called Neutrophil Extracellular Traps (or NETs), a defense system again pathogens possibly involving proteins with metal chelating properties. In order to gain insight in metal transport during this process, precise local evaluation of elemental content was performed reaching limits of detection (LODs) of 1 ppb. Mean weight fractions within entire neutrophils, their nuclei and cytoplasms were determined for the three main elements P, S and Cl, but also for the 12 following trace elements: K, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Br, Sr and Pb. Statistical analysis, including linear regression provided objective analysis and a measure for concentration changes. The nearly linear Ca and Cl concentration changes in neutrophils could be explained by already known phenomena such as the induction of Ca channels and the uptake of Cl under activation of NET forming neutrophils. Linear concentration changes were also found for P, S, K, Mn, Fe, Co and Se. The observed linear concentration increase for Mn could be related to scavenging of this metal from the pathogen by means of the neutrophil protein calprotectin, whereas the concentration increase of Se may be related to its antioxidant function protecting neutrophils from the reactive oxygen species they produce against pathogens. We emphasize synchrotron radiation based nanoscopic X-ray fluorescence as an enabling analytical technique to study changing (trace) element concentrations throughout cellular processes, provided accurate sample preparation and data-analysis.     

Ebselen augments its peroxidase activity by inducing nrf-2-dependent transcription

Ebselen is an organoselenium compound that acts as a glutathione peroxidase mimic. Since ebselen is a hydrophobic, thio-reactive compound capable of interacting with Keap-1, we tested its ability to activate nrf-2-dependent responses in the human hepatocarcinoma derived cell line, HepG2. Ebselen (25 microM) increased expression of an nrf-2 response element reporter in transient transfection experiments by 4-fold. Although, the induction was lower than that observed with classic nrf-2 inducer, sulforaphane (10 microL; 7-fold), ebselen also induced expression of native NAD(P)H:quinone oxidoreductase (1.6-fold) activity; induction of this protein is known to be dependent on nrf-2 action. Treatment of HepG2 cells with ebselen increased glutathione levels after 12 (1.5-fold) or 24 (1.9-fold)h of treatment. Treatment of the cells with either sulforaphane or ebselen 24 h prior to treatment with varying concentrations of t-butyl hydroperoxide increased the half maximal lethal dose from 28 to 42 microM and 58 microM for sulforaphane and ebselen, respectively. The protective effects of ebselen treatment were greater with pretreatment (IC50=58 microM) than simultaneous addition (IC50=45 microM). The protein synthesis inhibitor cycloheximide blocked increases in intracellular glutathione synthesis and partially blocked the protective effects of this regimen on increasing cell survival following t-butyl hydroperoxide treatment. Likewise co-treatment with the MEK 1 inhibitor, PD98059, which has been shown to inhibit nrf-2-dependent gene activation, partially inhibited the ebselen-dependent increases in IC50 while not affecting the control cells. We conclude that nrf-2 activation augments the role of ebselen as an antioxidant or by indirect induction of cellular antioxidant defences.     

Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases

Recently emerged viral infectious diseases (VIDs) include HIV/AIDS, influenzas H5N1 and 2009 H1N1, SARS, and Ebola hemorrhagic fevers. Earlier research determined metabolic oxidative stress in hosts deficient in antioxidant selenium (Se) (<1 μMol Se/L of blood) induces both impaired human host immunocompetence and rapidly mutated benign variants of RNA viruses to virulence. These viral mutations are consistent, rather than stochastic, and long-lived. When Se-deficient virus-infected hosts were supplemented with dietary Se, viral mutation rates diminished and immunocompetence improved. Herein is described the role of micronutrient Se deficiency on the evolution of some contemporary RNA viruses and their subsequent VIDs. Distinguishing cellular and biomolecular evidence for several VIDs suggests that environmental conditions conducive to chronic dietary Se deprivation could be monitored for bioindicators of incipient viral virulence and subsequent pathogenesis.     

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

Catalytic properties and cellular effects of the glutathione peroxidase (GPx)-mimetic compound PhSeZnCl or its d,l-lactide polymer microencapsulation form (M-PhSeZnCl) were investigated and compared with the prototypical Se-organic compounds ebselen and diselenide (PhSe)₂. PhSeZnCl was confirmed to catalyze the ping-pong reaction of GPx with higher V_max than ebselen and (PhSe)₂, but the catalytic efficiency calculated for the cosubstrates glutathione (GSH) and H₂O₂, and particularly the high reactivity against thiols (lowest K_M for GSH in the series of test molecules), suggested poor biological applicability of PhSeZnCl as a GPx mimetic. Cytotoxicity of PhSeZnCl was demonstrated in various cancer cell lines via increased reactive oxygen species (ROS) generation, depletion of intracellular thiols, and induction of apoptosis. Experiments carried out in GSH S-transferase P (GSTP)-overexpressing K562 human erythroleukemia cells and in GSTP1-1-knockout murine embryonic fibroblasts (MEFs) demonstrated that this cytosolic enzyme represents a preferential target of the redox disturbances produced by this Se-compound with a key role in controlling H₂O₂ generation and the perturbation of stress/survival kinase signaling. Microencapsulation was adopted as a strategy to control the thiol reactivity and oxidative stress effects of PhSeZnCl, then assessing applications alternative to anticancer. The uptake of this “depowered” GPx-mimetic formulation, which occurred through an endocytosis-like mechanism, resulted in a marked reduction of cytotoxicity. In MCF-7 cells transfected with different allelic variants of GSTP, M-PhSeZnCl lowered the burst of cellular ROS induced by the exposure to extracellular H₂O₂, and the extent of this effect changed between the GSTP variants. Microencapsulation is a straightforward strategy to mitigate the toxicity of thiol-reactive Se-organic drugs that enhanced the antioxidant and cellular protective effects of PhSeZnCl. A mechanistic linkage of these effects with the expression pattern and signaling properties of GSTP . This has overcome the GPx-mimetic paradigm proposed for Se-organic drugs with a more pragmatic concept of GSTP signaling modulators.     

Antioxidant Responses of Wheat Seedlings to Exogenous Selenium Supply Under Enhanced Ultraviolet-B

The paper reports the effects of selenium (Se) supply on growth and antioxidant traits of wheat (Triticum aestivum L. cv Han NO.7086) seedlings exposed to enhanced ultraviolet-B (UV-B) stress. Antioxidant responses of seedlings were different depending on the Se concentration. Compared with the control, the lower amount used (0.5 mg Se kg⁻¹ soil) had no significant effect on biomass accumulation. The treatments with 1.0, 2.0, and 3.0 mg Se kg⁻¹ promoted biomass accumulation of wheat seedlings, and the increased amount in biomass was the most at 1.0 mg Se kg⁻¹ treatment. Se treatments with 1.0, 2.0, and 3.0 mg kg⁻¹ also significantly increased activities of peroxidase (POD) and superoxide dismutase (SOD) and reduced the rate of superoxide radical (O₂⁻) production and malondialdehyde (MDA) content of wheat seedlings. In addition, anthocyanins and phenolic compounds content in wheat seedlings evidently increased by the treatments with 1.0 and 2.0 mg Se kg⁻¹. The lower Se treatment had no significant effect on MDA content, although it increased activities of antioxidant enzymes (POD, SOD, and catalase activities) and reduced the rate of O₂⁻ production in wheat seedlings. These results suggest that optimal Se supply is favorable for the growth of wheat seedlings and that optimal Se supply can reduce oxidative stress of seedlings under enhanced UV-B radiation.     

X-Ray Fluorescence Microscopy Reveals the Role of Selenium in Spermatogenesis

Selenium (Se) is a trace element with important roles in human health. Several selenoproteins have essential functions in development. However, the cellular and tissue distribution of Se remains largely unknown because of the lack of analytical techniques that image this element with sufficient sensitivity and resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be used to visualize and quantify the tissue, cellular, and subcellular topography of Se. We applied this technique to characterize the role of Se in spermatogenesis and identified a dramatic Se enrichment specifically in late spermatids, a pattern that was not seen in any other elemental maps. This enrichment was due to elevated levels of the mitochondrial form of glutathione peroxidase 4 and was fully dependent on the supplies of Se by selenoprotein P. High-resolution scans revealed that Se concentrated near the lumen side of elongating spermatids, where structural components of sperm are formed. During spermatogenesis, maximal Se associated with decreased phosphorus, whereas Zn did not change. In sperm, Se was primarily in the midpiece and colocalized with Cu and Fe. XFM allowed quantification of Se in the midpiece (0.8 fg) and head (0.2 fg) of individual sperm cells, revealing the ability of sperm cells to handle the amounts of this element well above its toxic levels. Overall, the use of XFM allowed visualization of tissue and cellular Se and provided important insights in the role of this and other trace elements in spermatogenesis.     

Mechanisms of selenium hyperaccumulation in plants: A survey of molecular,biochemical and ecological cues

Background

Selenium (Se) is a micronutrient required for many life forms, but toxic at higher concentration. Plants do not have a Se requirement, but can benefit from Se via enhanced antioxidant activity. Some plant species can accumulate Se to concentrations above 0.1% of dry weight and seem to possess mechanisms that distinguish Se from its analog sulfur (S). Research on these so-called Se hyperaccumulators aims to identify key genes for this remarkable trait and to understand ecological implications.

Selenium distribution in ryegrass and its antioxidant role as affected by sulfur fertilization

Selenium (Se) essentiality to plants has not been demonstrated although evidence indicates that it plays a significant role as antioxidant in higher plants. Research concerning to the uptake and allocation of Se in plant tissues is reported in numerous works. However, the effect of sulfur (S) on both the distribution and the antioxidant ability of Se in selenite-treated plant remains unclear. In this work the effect of S application (0–100 mg S kg⁻¹ soil) on shoot Se concentration of Lolium perenne cv. Aries was studied. Se distribution into different fractions of plants supplied with selenite (2 mg Se kg⁻¹ soil) and the state of the antioxidative system were determined. Results showed that shoot Se concentration decreased at least 33% by S application. Plants supplied with S registered the lowest GSH-Px activity and the highest lipid peroxidation. Most of Se was incorporated into the organic fraction of the plant tissue irrespective of the S treatment. However, a significant decrease of both the soluble protein and the amino acid fraction occurred, and the residual Se fraction seemed to increase at expense of the organic-Se soluble fraction. Although no essential selenoproteins have been clearly identified in vascular plants, the decrease of the soluble protein fraction and the different pattern of protein synthesized (SDS-PAGE analysis) may explain the observed reduction of the GSH-Px activity.     

Accumulation and volatilization of different chemical species of selenium by plants

Selenium (Se) removal from polluted waters and soils is especially complicated and highly expensive. Phytoremediation has been suggested as a low-cost, efficient technology for Se removal. Plants remove Se by uptake and accumulation in their tissues, and by volatilization into the atmosphere as a harmless gas. Unraveling the mechanisms of Se uptake and volatilization in plants may lead to ways of increasing the efficiency of the phytoremediation process. The objectives of this study were: (i) to determine the effect of different Se forms in the root substrate on the capacity of some plant species to take up and volatilize Se; (ii) to determine the chemical species of Se in different plant parts after the plants were supplied with various forms of Se; and (iii) to determine the influence of increasing sulfate levels on plant uptake, translocation, and volatilization of different Se species. Plants of broccoli (Brassica oleracea var. botrytis L.), Indian mustard (Brassica juncea L.), sugarbeet (Beta vulgaris L.) and rice (Oryza sativa L.) were grown hydroponically in growth chambers and treated for 1 week with 20 μM Se as Na₂SeO₄, Na₂SeO₃ or L-selenomethionine (SeMeth) and increasing sulfate levels. The data show that shoots of SeO₄-supplied plants accumulated the greatest amount of Se, followed by those supplied with SeMeth then SeO₃. In roots, the highest Se concentrations were attained when SeMeth was supplied, followed by SeO₃, then SeO₄. The rate of Se volatilization by plants followed the same pattern as that of Se accumulation in roots, but the differences were greater. Speciation analysis (X-ray absorption spectroscopy) showed that most of the Se taken up by SeO₄-supplied plants remained unchanged, whereas plants supplied with SeO₃ or SeMeth contained only SeMeth-like species. Increasing the sulfate level from 0.25 mM to 10 mM inhibited SeO₃ and SeMeth uptake by 33% and 15–25%, respectively, as compared to an inhibition of 90% of SeO₄ uptake. Similar results were observed with regard to sulfate effects on volatilization. We conclude that reduction from SeO₄ to SeO₃ appears to be a rate-limiting step in the production of volatile Se compounds by plants. Inhibitory effects of sulfate on the uptake and volatilization of Se may be reduced substantially if Se is supplied as, or converted to, SeO₃ and/or SeMeth rather than SeO₄. Received: 27 February 1998 / Accepted: 30 March 1998     

Cytoprotection against lipid hydroperoxides correlates with increased glutathione peroxidase activities, but not selenium uptake from different selenocompounds

Cells cultivated under standard conditions were highly deficient in tocopherol, selenium, and glutathione peroxidase (GPx) activities. We investigated whether and to what extent the addition of different selenocompounds to growth media would alter biochemical, physiological, and pathophysiological parameters of cultured liver cells. Cellular uptake of selenium, GPx activities, and cytoprotection were measured and compared in human hepatoma cells (HepG2). Selenite and selenocystine were Se donors of high bioavailability (i.e., with these culture supplements, the increased Se uptake, induction of GPx isoenzymes, and protection of treated cells from lipid hydroperoxides were well correlated). In contrast, selenium from selenomethionine was incorporated into cellular proteins but had no effect on GPx activities or cytoprotection. The data show that not all selenium donors provide selenium, which is bioactivated to act as antioxidant. Thus, cellular selenium content, in general, did not correlate with cytoprotective activity of this trace element. However, cellular GPx activities at different times, with different concentrations, and with different Se donors always correlated with protection from lipid hydroperoxides and may, thus, represent a more reliable parameter to define adequate Se supply.     

Protective role of selenium in wheat seedlings subjected to enhanced UV-B radiation

Selenium (Se) is beneficial for some plants and is able to increase resistance and antioxidant capacity of plants subjected to stressful environment. In this work, the effects of enhanced ultraviolet-B (UV-B) radiation, Se supply, and their combination on growth and physiological traits of wheat (Triticum aestivum L., cv. Han NO.7086) seedlings were studied. The objective was to elucidate whether Se could alleviate the expected adverse effects of UV-B stress on seedlings. UV-B treatment caused a marked decline in growth parameters and total chlorophyll content and changed biomass allocation between aboveground and underground parts, which led to an increase in the root/shoot ratio. UV-B treatment also increased MDA content and the rate of superoxide radical (O₂^·−) production, although it increased some antioxidant (proline, phenolic compounds, and flavonoids) content and activity of antioxidant enzymes (peroxidase, superoxide dimutase, catalase (CAT)). Se treatment only increased total chlorophyll content and CAT activity. Compared with UV-B treatment alone, the combined treatment with UV-B and Se induced a significant increase in the biomass, total chlorophyll content, antioxidant content, and activity of antioxidant enzymes, and an evident decrease in MDA content and the rate of O₂^·− production. The results of this study demonstrated that Se alleviated the damage caused by UV-B to wheat seedlings to some extent by increasing antioxidant enzyme activity and antioxidant content.     

Vitamin E and selenium administration as a modulator of antioxidant defense system: biochemical assessment and modification

Exposure of cells to ionizing radiation leads to the formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. Because of the serious damaging potential of ROS, cells depend on the elaboration of the antioxidant defense system (AODS), both enzymatic and nonenzymatic oxidant defense mechanisms. The deficiency in important components of the endogenous AODS leads to the accumulation of oxidative stress inducing oxidative damage. The antioxidant enzymes superoxide dismutase and glutathione peroxidase are key intracellular antioxidants in the metabolism of ROS. In the current study, we investigated the potential role of these antioxidant enzymes in radioresistance during the evaluation of the compensatory role of some exogenous micronutrients against oxidative stress Animals were categorized into eight groups, receiving vitamin E (α-tocopherol) and/or selenium (Se) with or without whole-body γ-irradiation (6.5 Gy). The results indicate that antioxidant pretreatments before irradiation may have some beneficial effects against irradiation-induced injury. The results also indicate that selenium and vitamin E act alone and in an additive fashion as radioprotecting agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown, whereas vitamin E appears to confer its protection by an alternate complementary mechanism.     

Responses of Wheat Seedlings to Exogenous Selenium Supply Under Cold Stress

Dose-dependent effects of selenium on growth and physiological trait of wheat seedlings (Triticum aestivum L. cv Han NO.7086) exposed to cold stress are reported. Responses of seedlings were different depending on the Se concentration. The treatments with 0.5 and 1.0 mg Se kg⁻¹ significantly increased biomass and chlorophyll content of seedlings. However, the treatments at 2.0 and 3.0 mg Se kg⁻¹ only induced an evident increase in chlorophyll content and did not promote biomass accumulation of seedlings. Antioxidant compounds content (anthocyanins, flavonoids, and phenolic compounds) and antioxidant enzymes’ activities (peroxidase and catalase) increased by different Se treatments, while only the treatment with 1.0 mg Se kg⁻¹ induced a significant reduce in malondialdehyde content and the rate of superoxide radical production of wheat seedlings. The results of this study demonstrated that Se supply could increase antioxidant capacity of seedlings, and optimal Se supply reduced production of free radicals, membrane lipid peroxidation, and promoted biomass accumulation.     

Oxidative Stress Induced by Cadmium in the C6 Cell Line: Role of Copper and Zinc

In this report, we have investigated the role of copper (Cu) and zinc (Zn) in oxidative stress induced by cadmium (Cd) in C6 cells. Cells were exposed to 20 μM Cd, 500 μM Cu, and 450 μM Zn for 24 h. Then, toxic effects, cellular metals levels, oxidative stress parameters, cell death, as well as DNA damage were evaluated. Cd induced an increase in cellular Cd, Cu, and Zn levels. This results not only in the inhibition of GSH-Px, GRase, CAT, and SOD activities but also in ROS overproduction, oxidative damage, and apoptotic cell death not related to Cu and Zn mechanisms. The thiol groups and GSH levels decreased, whereas the lipid peroxidation and DNA damage increased. The toxicity of Zn results from the imbalance between the inhibition of antioxidant activities and the induction of MT synthesis. The increase in Cu and Zn levels could be explained by the disruption of specific transporter activities, Cd interference with signaling pathways, and metal displacement. Our results suggest that the alteration of Cu and Zn homeostasis is involved in the oxidative stress induced by Cd.