Glutathione Peroxydase Research Articles

Investigation of malondialdehyde, catalase, glutathione peroxydase and FRAP as biomarker for oxidative stress linked to hyperuricemia in a sub-Saharan population with heart failure

Investigation of malondialdehyde, catalase, glutathione peroxydase and FRAP as biomarker for oxidative stress linked to hyperuricemia in a sub-Saharan population with heart failure

Fluctuating asymmetry of sclerotized structures of Haliotrematoides spp. (Monogenea: Dactylogyridae) as bioindicators of aquatic contamination

Abstract Fluctuating asymmetry (FA) and increased variation in bilateral symmetry in a sample of monogeneans can indicate disturbance in developmental stability caused by environmental and/or genomic stress. This study was conducted to determine the presence of FA in the sclerotized structures of Haliotrematoides spp. (Monogenea) collected along the continental shelf of the Yucatan Peninsula. We hypothesize the potential effect of chemical contamination on FA. Geometric morphometrics with Procrustes ANOVA was used to test FA in the ventral and dorsal anchors in Haliotrematoides spp. Then, Generalized Additive Model for Location, Scale and Shape (GAMLSS) were used to assess the statistical associations of heavy metal concentrations, Polycyclic Aromatic Hydrocarbons (PAHs), gene expression, PAHs metabolites in bile, fish morphometric measurements, physicochemical and spatial variables on FA patterns. Principal Component Analysis showed no clear group formation according to shape variability by sampling site. Evidence of FA for size and shape in ventral anchors of Haliotrematoides striatohamus was found, in contrast to dorsal anchors, which only displayed shape FA. For Haliotrematoides sp. only evidence for shape FA of ventral and dorsal anchors was found. The GAMLSS models revealed a significant positive relationship between the FA of Haliotrematoides spp. and PAHs, Pb, Naphthalene, Ni, pH, Hydroxy-Phenanthrene, Depth, DNA Methylation, Glutathione peroxydase and Condition factor (K). These results partially support our hypothesis that FA in the anchors would be produced by aquatic contamination but in association to other environmental variables and host related factors.

A New Role of Glutathion Peroxydase 4 in Human Erythroblast Enucleation

The Gluthation peroxidase (GPX) enzymes are part of the protective system against lipid peroxydation that includes prevention of oxydation and reduction of already oxidized lipid through enzymatic reactions catalyzed by GSH. GPX4 is one of the five GPX able to incorporate selenium. It is also the only GPX able to directly reduce in the membrane the oxidized fatty acids and cholesterol. Recent reports identified GPX4 as the central inhibitor of ferroptosis, a process during which iron-induced peroxydation of membrane lipids causes a specific cell death that can be reverted by lipophilic antioxydants or by iron chelators. GPX4 has recently been involved during mice erythropoiesis: GPX4-/-mice present a hemolytic anemia and a high apoptotic rate in spleen erythroid progenitors. Although transcriptomics and proteomics found it expressed in human erythroid precursors, its role during human erythropoiesis has not been described. Using an in-vitroerythroid differentiation protocol from CD34+cells obtained from apheresis, we confirmed that GPX4 expression was induced at RNA and protein level during differentiation. RSL3, a specific GPX4 inhibitor, didn't affect early steps of erythropoiesis (i.eclonogenic potential and progenitor amplification) nor the early maturation of erythroid precursors (assessed by sequential CD49d/CD235/CD71 staining) but led to a significant decrease in the enucleation rate as assessed by Hoechst staining using flow cytometry (74%±9 DMSO versus 35%±6 RSL3, p<0.01) and by cytology after MGG staining (58%±10 DMSO versus 27% RSL3±5, p<0.05). This effect was not related to ferroptosis since (i) FIN56 and erastin, two other ferroptosis activators, didn't impact enucleation and (ii) the enucleation defect was not reverted by tocopherol or ferrostatin. Of note, tocopherol reverted lipid peroxydation at cell surface, as shown by Bodipy-C11 staining, showing that enucleation defect and lipid peroxydation were not directly related. These data argue for a specific GPX4 role in the enucleation process, independently to its well-described function in ferroptosis control. Using Western Blot, we observed that RSL3 exposure induced a strong GPX4 depletion in erythroid progenitors while it didn't affect GPX1, another member of the GPX family expressed in erythroid cells. In order to confirm that enucleation defect was related to GPX4 knockdown, we used an Sh-RNA strategy that allowed a 62%±6 GPX4 decrease at RNA level and a 46%±5 at protein level. We observed a significant defect in terminal enucleation in the cells transduced with shGPX4-lentiviruses in comparison with sh-Scramble (59%±5 Sh-Scr versus 39%±6 Sh-Gpx4, p<0.05). Isopentylpyrophosphate, an intermediate component of cholesterol synthesis that also acts as a substract of selenoprotein synthesis, restored partially both GPX4 expression and erythroblast enucleation. We investigated then whether GPX4-knock-down affected quantitatively or qualitatively the membrane lipid content, which was shown to be involved in the enucleation process. Addition of Cholesterol to RSL3 in the medium partially restored the enucleation rate. However, lipidomics failed to show any significant difference in the total membrane lipid content (and particularly in the cholesterol content) after RSL3 exposure in comparison to DMSO. Since cholesterol is particularly abundant in the lipid rafts, we investigated whether the lipid distribution was qualitatively altered within the cell membrane. We observed a disruption of membrane lipid rafts when cells were exposed to RSL3, as shown by a 60%±12 decrease in the mean cholera toxin fluorescence intensity. GPX4 presence in lipid rafts was confirmed using immunofluorescence showing their co-localization at cell surface in human primary erythroblasts. Since lipid rafts play a role in the contractile ring that separates pyrenocyte from reticulocyte, we evaluated the myosin-light chain phosphorylation using flow cytometry and Western Blot and found it drastically decreased in GPX4-knockdown conditions. In summary, we identified GPX4 as a new actor of human terminal erythroid differentiation, independently to its function in ferroptosis control. We described its interaction at cell surface with lipid rafts that are required for the assembly of the contractile ring and cytokinesis leading to the nucleus extrusion. Disclosures No relevant conflicts of interest to declare.

ERYTHROPOIETIN NEUROPROTECTIVE PROPERTY AS NEW AS THERAPEUTIC TOOL FOR APNEA OF PREMATURITY

We tested the hypothesis that Epo (Erythropoietin) protects newborns against the consequences of IH induced by apnea of prematurity (AoP). As caffeine (despite ineffective in about 50% of cases) is the treatment of choice of AoP, the effect of Epo and caffeine was compared.Male and female newborn rats exposed to IH during postnatal days (P) 3–10 were used in this work. During this time, animals were daily gavage with vehicle, Epo, caffeine, and Epo+caffeine (10–12 pups/group). At P10 the frequency of apneas and mean duration of apnea at rest were measured (as index of respiratory dysfunction induced by IH) plethysmography. Next, the hippocampus, cortex, and brainstem were harvested, and the activity of Superoxide‐Dismutase (SOD – major anti‐oxidant), Glutathion peroxydase (GPx) and NADPH oxidase (NOX – major pro‐oxidant) enzymes were evaluated.Our results showed that IH increased the frequency of apnea and mean duration of apnea in male and female, reduced SOD anf GPx activity, but increased NOX activity. Interestingly, Epo and caffeine significantly reduced apnea frequency, but only Epo efficiently restored the oxidant activity to normal levels. Moreover, the administration of Epo and caffeine together provided cumulative beneficial effects in reducing the apneic episodes in male and female pups.We conclude that Epo and caffeine activate different, but complementary mechanisms to decrease apneas, suggesting that combined Epo+caffeine treatment could be clinically relevant against AoP.Support or Funding InformationFounded by CIHR, Région Rhône alpes and consulat de France à Québec.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Plasma Levels of Selenium (SE) and Glutathion Peroxydase (GSH-PX) and their Relationship to Supplementation of Selenium in Patients with Chronic Renal Failure (CRF) on Hemodialysis (HD)

Introduction: Plasma levels of Se and GSH-Px decrease with the progression of renal impairment and is particularly pronounced at the end stage of chronic kidney disease (CKD) as kidney proximal tubular cells are the main source of pGSH-Px activity. A number of authors found that Se supplementation increases its plasma levels in patients on HD, but publications about influence of Se supplementation on plasma GSH-Px are controversial-from a lack of any effect to a significant increase of the enzyme. The study aims to monitor levels of plasma selenium (pSe) and glutathione peroxidase (pGSH-Px) in patients on HD treatment with Se deficit, orally supplemented with Se for 3 months, and to evaluate the supplementation on pSe and pGSH-Px. Material and Methods: 61 patients on regular hemodialysis, divided into two groups (1st group-33 pts. with pSe deficit and, 2nd group-28 with normal pSe levels) were tested at the beginning of dialysis sessions for serum hemoglobin, total protein, albumin, creatinine, urea, uric acid, C-reactive protein (CRP), phosphorus, potassium plasma Se and pGSH-Px activity. The same parameters were re-examined at the end of the study. The patients of the 1st group were supplemented with oral Se for 3 months and the results in the two groups were compared. Results: All parameters (except pSe and pGSH-Px in the 1st group) showed no significant differences in the beginning and the end of the follow-up period in both patients groups. The levels of pSe and pGSH-Px in the 2nd group also showed no significant change, but in the 1st group both parameters increased significantly at the end of the 3-months period. We found a significant correlation between pSe/pGSH-Px (p<0.01), and between pGSH-Px/Creatinine (p<0.01) at the start and the end of the study. Conclusion: Our study suggests that supplementation of oral Se in patients with CKD on regular HD, significantly increases not only pSe, but pGSH-Px as well, despite a proved presence of bilateral nephrosclerosis in all patients of both groups. As a positive effect, at least one of the members of anti-oxidant system in this patients contingent is enhanced, namely pGSH-Px.

Correlation of trans fatty acids with the severity of coronary artery disease lesions

BackgroundNutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index.MethodsFatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied.ResultsOur study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes.ConclusionsHigh level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Ageing process and sapropelic mud from Techirghiol lake

Aging represents the expression of a progressive functional imbalance of the neuroendocrine system and antioxidant status. The aim of this study was to investigate some determining factors: insulin 1 growth factor (IGF-1), serum cortisol, dehydroepiandrosterone-sulfate (DHEA-S), glutathione-peroxydase (GPx), that seem to play a major role in the beginning and evolution of the biological ageing process and their behaviour under the effect of peloidotherapy.

Protective Effects of Dietary Garlic Powder Against Cadmium-induced Toxicity in Sea Bass Liver: a Chemical, Biochemical, and Transcriptomic Approach.

To investigate the protective effect of garlic powder on cadmium-induced toxicity sea bass liver, juvenile fishes where maintained under three food diets (diet 1: normal without garlic supply, diet 2: 2% garlic powder; diet 3: 6% garlic powder). After 30days of specific diets, each group was injected with 500μgkg-1of Cd. The control group was the one fed with normal diet and not injected with Cd. Liver Cd, Zn, and Se loads was assessed after 1 and 3days of Cd injections. Moreover, antioxidant enzymes activities termed as catalase, superoxide dismutase, and glutathione peroxydase as well as their gene expression levels were monitored. Finally, metallothionein protein accumulation and its gene expression regulation (MTa) were determined. In fish fed with 2 and 6% garlic powder, the amounts of Cd, Zn, and Se significantly increase in liver tissues. Two percent garlic powder specific diet reversed the Cd-induced inhibition of catalase (CAT), superoxide dismutase (SOD), and gluthathione peroxydase (GPx) and restored the Cd-induced lipid peroxidation (MDA). The increase of liver metallothionein proteins as well as the MTa gene expression level under Cd influence was more pronounced in animals maintained for 30days under garlic power 2% diet. Our data must be carefully considered in view of the garlic powder introduction in sea bass food composition at 2% since it is an efficient prevention against Cd-induced alterations.

Activity of key enzymes of antioxidant system in rat blood plasma under the effect of histamine and sodium hypochlorite

The effects of histamine in 1 mg/kg and 8 mg/kg doses that correspond to the doses causing pathological effects at experimental conditions and of sodium hypochlorite in 5 mg/l dose – the lowest concentration of sodium hypochlorite that affects a body by oral administration, on the key enzymes of blood plasma antioxidant system were studied. It was found that histamine used in both concentrations intensified superoxide dismutase activity for 14 days. The simultaneous injections of histamine and sodium hypochlorite caused significant activation of superoxide dismutase in rats. Sodium hypochlorite received by rats with drinking solution caused the same effect. The catalase activity of blood plasma was not significantly affected by histamine, and its activity was significantly increased only under the influence of biogenic amine in 1 mg/kg dose on the 7 th day of the experiment. Sodium hypochlorite caused a decline in catalase activity both in intact animals and in animals that received histamine injections subcutaneously. The injection of histamine in 1 mg/kg dose caused an increase in glutathione peroxidase activity on the 1 st and 7 th day of the experiment. Histamine in 8 mg/kg dose caused the intensification of glutathione peroxidase activity only on the 1 st day, followed by the inhibition on the 14 th day of the experiment. Sodium hypochlorite received by rats with drin­king solution led to general lowering of glutathione peroxydase activity in blood plasma.

Sublethal effect assessment of a low-power and dual-frequency anti-cyanobacterial ultrasound device on the common carp (Cyprinus carpio): a field study.

The use of ultrasonication for cyanobacterial control in freshwater bodies has become increasingly popular during the last decades despite controversial efficiency on large scale application. Apart from that, little information is currently available regarding ultrasound toxicity potential towards non-target species. This work was designed to address this issue in the common carp using a low-power (7-9W output) and dual-frequency (23 and 46kHz) anti-cyanobacterial ultrasound device. Results showed that carps were unaffected by ultrasound exposure when exposed in floating cages in fish ponds over a 30-day period. The experiment duration was the main factor influencing all measured biological parameters in exposed and non-exposed organisms. Indeed, it was positively associated with an increase in fish condition factor. Cortisol level also tended to slightly increase over the number of days of experiment but its variation did not enable to sort out any ultrasound exposure-related stress. Moreover, an overall diminution along the experimental period of the expression level of a set of biomarkers could be reported, encompassing cellular antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione peroxydase (GPx), catalase and glutathione S-transferase (GST), and lactate dehydrogenase activity. Subtle changes in these biomarkers were dependent of the type of enzyme activity and especially of the origin of fish (i.e., sampled pond) regardless of the presence of ultrasound equipment, reflecting thereby fish adaptation to local environmental conditions in each pond. In conclusion, this study does not provide indication that ultrasonication in the aforementioned conditions affects the welfare and physiological homeostasis of carps.

Abstract LB-334: The Nrf2-subcellular localization in human acute myeloblastic leukemic cells is regulated by the bone marrow mesenchymal stem/stromal cells

Abstract BACKGROUND. The redox metabolism is a key actor in the pathophysiology of acute myeloblastic leukemia (AML). High level of reactive oxygen species (ROS) is observed in the leukemic bulk, whereas leukemic stem cells (LSCs) have a low level of ROS, and we reported that glutathione peroxydase 3 (GPx-3) promotes competitiveness of LSCs in which Gpx3 overexpression is associated with a decreased level of ROS and inactivation of p38 MAPK (Herault O et al, J Exp Med 2012, 209:895). NF-E2-related factor 2 (Nrf2) transcription factor, the master regulator of antioxidant responses, is highly expressed in acute myeloblastic leukemia (AML) and is involved in its chemoresistance (Rushworth SA et al, Blood 2012, 120,5188). Since leukemic cells interact with mesenchymal stem/stromal cells (MSCs) in the bone marrow (BM) niche, the aim of our study was to evaluate the effects of MSC-contact on the Nrf2 sub-cellular localization in acute myeloid leukemia (AML) cells and to concomitantly assess the the GPx-3/ROS/p38 MAPK axis and cell cycle status. METHODS. BM MSCs (from consenting patients undergoing orthopaedic surgery) were used at P2. The mesenchymal differentiation capacity was systematically checked. The KG1a (FAB M0 AML) cell line and primary AML blasts were cultured for 72h in presence of MSCs and compared to their counterpart cultured in presence of supernatant from MSCs alone or medium alone. ROS level measurements (DCFDA), cell cycle analyses (Vignon C et al, PLOS One 2013, 8: e68425) and proliferation assays (CFSE) of the leukaemic cells were performed by flow cytometry. Expression levels of 24 key antioxidant genes, CDKN1A (p21, Cip1) and 22 Nrf2-regulated genes were quantified by qRT-PCR. Western-blot analyses were also realized to determine the expression levels of GPx-3 and p21(Cip1), the activation of p38 MAPK (T180/Y182) and the localization of Nrf2 after subcellular fractionation. RESULTS. Adherent KG1a cells were characterized by major decrease in nuclear translocation of Nrf2 and expression of Nrf2-regulated genes. We concomitantly observed overexpression of GPX3 mRNA and protein, major decrease in ROS levels and inactivation of p38 MAPK. Similar results were obtained with adherent primary leukemic cells. These effects were concomitantly observed with major decrease in nuclear translocation of Nrf2 and expression of Nrf2-regulated genes. Interestingly, the increased G0 phase, together with the decreased S and M phases, and overexpression of CDKN1A mRNA and protein demonstrated cell cycle inhibition and reduced mitotic activity. The supernatant of MSCs did not impact on Nrf2-subcellular localization, GPx-3 expression and ROS levels in leukemic cells. CONCLUSION. Altogether these findings suggest that the niche (direct contact to MSCs) plays a key role in the regulation of the oxidative metabolism in leukemic cells by modifying the subcellular localization of Nrf2 and by promoting the inhibition of the ROS/p38 MAPK axis through the induction of GPx-3, resulting in a reduced proliferation. Targeting the Nrf2 pathway in leukemic cells by a modulation of microenvironmental interactions may be a clinically relevant chemosensitizing approach. Citation Format: Olivier Herault, Christine Vignon, Christelle Debeissat, Florence Rouleux-Bonnin, Emmanuel Gyan, Frederic Mazurier, Fabrice Gouilleux, Jorge Domenech. The Nrf2-subcellular localization in human acute myeloblastic leukemic cells is regulated by the bone marrow mesenchymal stem/stromal cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-334.

Putative anticancer potential of novel 4-thiazolidinone derivatives: cytotoxicity toward rat C6 glioma in vitro and correlation of general toxicity with the balance of free radical oxidation in rats.

AimTo evaluate the cytotoxic action of 4-thiazolidinone derivatives (ID 3288, ID 3882, and ID 3833) toward rat glioma C6 cells and to compare the effects of these compounds and doxorubicin on the balance of free radical oxidation (FRO) and antioxidant activity (AOA) in the serum of rats.MethodsGlioma cells were treated with ID 3882, ID 3288, ID 3833, and doxorubicin, and their cytotoxicity was studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Trypan blue exclusion test, light and fluorescent microscopy, and flow cytometric study of cell cycling and apoptosis, including measuring of Annexin V-positive cells. The contents of superoxide radical, hydrogen peroxide, hydroxyl radical, malonic dialdehyde, and hydrogen sulfide were measured in the serum of rats. Enzymatic activity of superoxide dismutase (SOD), catalase (Cat), and glutathione peroxydase (GPO) was determined.ResultsAmong novel 4-thiazolidinone derivatives, ID 3288 was most toxic toward rat glioma C6 cells, even compared with doxorubicin. All applied derivatives were less active than doxorubicin in inducing reactive oxygen species-related indicators in the serum of rats. A similar effect was observed when enzymatic indicators of AOA processes were measured. While doxorubicin inhibited the activity of SOD, GPO, and Cat, the effects of 4-thiazolidinone derivatives were less prominent.ConclusionNovel 4-thiazolidinone derivatives differ in their antineoplastic action toward rat glioma C6 cells, and ID 3288 possesses the highest activity compared to doxorubicin. Measurement of indicators of FRO and AOA in the serum of rats treated with these compounds showed their lower general toxicity compared with doxorubicin’s toxicity.

Impact of proline application on cadmium accumulation, mineral nutrition and enzymatic antioxidant defense system of Olea europaea L. cv Chemlali exposed to cadmium stress

Proline plays an important role in plant response to various environmental stresses. However, its involvement in mitigation of heavy metal stress in plants remains elusive. In this study, we examined the effectiveness of exogenous proline (10 and 20mM) in alleviating cadmium induced inhibitory effects in young olive plants (Olea europaea L. cv. Chemlali) exposed to two Cd levels (10 and 30mg CdCl2kg−1 soil). The Cd treatment induced substantial accumulation of Cd in both root and leaf tissues and a decrease in gas exchange, photosynthetic pigments contents, uptake of essential elements (Ca, Mg and K) and plant biomass. Furthermore, an elevation of antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxydase) and proline content in association with relatively high amounts of hydrogen peroxide, thiobarbituric acid reactive substances and electrolyte leakage were observed. Interestingly, the application of exogenous proline alleviated the oxidative damage induced by Cd accumulation. In fact, Cd-stressed olive plants treated with proline showed an increase of antioxidant enzymes activities, photosynthetic activity, nutritional status, plant growth and oil content of olive fruit. Generally, it seems that proline supplementation alleviated the deleterious effects of young olive plants exposed to Cd stress.

Exogenous proline mediates alleviation of cadmium stress by promoting photosynthetic activity, water status and antioxidative enzymes activities of young date palm (Phoenix dactyliferaL.)

The ability of exogenous compatible solutes, such as proline, to counteract cadmium (Cd) inhibitory effects in young date palm plants (Phoenix dactylifera L. cv Deglet Nour) was investigated. Two-year-old date palm plants were subjected for five months at different Cd stress levels (0, 10 and 30mg CdCl2kg−1 soil) whether supplied or not with exogenous proline (20mM) added through the irrigation water. Different levels of Cd stress altered plant growth, gas exchanges and chlorophyll content as well as water status, but at different extent among them. In contrast, an increase of antioxidant enzymes activities of Cd-treated plants in association with high amounts of proline content, hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) and electrolyte leakage (EL) were observed. Interestingly, exogenous proline mitigated the adverse effects of Cd on young date palm. Indeed, it alleviated the oxidative damage induced by Cd accumulation and established better levels of plant growth, water status and photosynthetic activity. Moreover, proline-treated plants showed high antioxidant enzymes activities (superoxide dismutase, catalase and glutathione peroxydase) in roots and leaves as compared to Cd-treated plants.

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio).

Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 βestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017.

Selenium status in cattle herds in Wallonia (Belgium): overview and health management

Aim: Monitoring was performed in order to determine the Selenium (Se) status of cattle herds in different agricultural areas in Wallonia (Belgium). Materials and Methods: The study included 114 heifers and 184 cows (82 dairy and 102 beef cows) from 66 cattle farms situated in Wallonia. The Se status was assessed by measuring the glutathion peroxydase in red cells and converting it to the equivalent Se blood content. Results: The average blood concentrations of Se were very low. The Ardennes region was an area where the lowest Se status was recorded. The highest levels of Se in dairy cows and beef cows were recorded respectively in the limoneuse region and Famenne areas. The Se content in beef herds was lower compared with that of dairy herds (35 vs. 56 μg/L, p<0.01). Conclusion: On average over all the regions, 87% of animals were classified as deficient and only 13% of the animals were classified as adequate. The heifers from both dairy and beef herds in Wallonia exhibited a deficiency in Se classified as moderate to severe. The beef herds showed larger deficiencies compared with the dairy herds. Selenium deficiency can be prevented by ensuring adequate supplementation of deficient animals in Se deficient regions. An increased consumption of vitamin-mineral supplements, the use of Se-enriched fertilizers and ingredients containing high levels of Se can help to reduce or correct deficiencies recorded in cattle herds in Wallonia.

Increased oxidative stress and altered levels of nitric oxide and peroxynitrite in Tunisian patients with chronic obstructive pulmonary disease: correlation with disease severity and airflow obstruction.

This study was aimed to evaluate the oxidant-antioxidant imbalance in the pathogenesis of chronic obstructive pulmonary disease (COPD) in Tunisians. We assessed 16 parameters related to the oxidative status that include malondialdehyde (MDA), total protein carbonyls (PCs), and advanced oxidation protein products (AOPP). We also examined the activity of glutathione peroxydase (GSH-Px), catalase, and superoxide dismutase (SOD) in the plasma and erythrocytes. Levels of total thiols, reduced glutathione (GSH), total antioxidant status (TAS), hydrogen peroxide, ascorbic acid, iron, and protein sulfhydryls were determined using spectrophotometry. We also evaluated the level of nitric oxide (NO) and peroxynitrite in plasma from COPD patients and healthy controls. Estimation of DNA damage was determined using the comet assay. Pulmonary functional tests were performed by body plethysmography. Levels of MDA, PC, DNA damage, and AOPP were significantly increased while total thiols, GSH, and TAS were decreased in COPD patients. GSH-Px activity was higher in COPD patients while no difference was found for catalase and SOD. We also observed a lower level of NO and peroxynitrite in COPD patients. Decreased levels of peroxynitrite were found to correlate with disease progression, as well as with forced expiratory volume in 1 s/forced vital capacity among COPD patients. Multivariate analysis revealed that NO is associated with pathological pathways that help to predict patient outcome independently of the degree of airflow obstruction. These results indicate the presence of a systemic oxidative stress and highlight the importance of NO and peroxynitrite as major effectors in COPD development and airflow obstruction.

Evidence of trophic transfer of microcystins from the gastropod Lymnaea stagnalis to the fish Gasterosteus aculeatus

According to our previous results the gastropod Lymnaea stagnalis exposed to MC-producing cyanobacteria accumulates microcystins (MCs) both as free and covalently bound forms in its tissues, therefore representing a potential risk of MC transfer through the food web. This study demonstrates in a laboratory experiment the transfer of free and bound MCs from L. stagnalis intoxicated by MC-producing Planktothrix agardhii ingestion to the fish Gasterosteus aculeatus. Fish were fed during five days with digestive glands of L. stagnalis containing various concentrations of free and bound MCs, then with toxin-free digestive glands during a 5-day depuration period. MC accumulation was measured in gastropod digestive gland and in various fish organs (liver, muscle, kidney, and gills). The impact on fish was evaluated through detoxification enzyme (glutathion-S-transferase, glutathion peroxydase and superoxyde dismutase) activities, hepatic histopathology, and modifications in gill ventilation, feeding and locomotion. G. aculeatus ingestion rate was similar with intoxicated and toxin-free diet. Fish accumulated MCs (up to 3.96±0.14μgg−1DW) in all organs and in decreasing order in liver, muscle, kidney and gills. Hepatic histopathology was moderate. Glutathion peroxydase was activated in gills during intoxication suggesting a slight reactive oxygen species production, but without any impact on gill ventilation. Intoxication via ingestion of MC-intoxicated snails impacted fish locomotion. Intoxicated fish remained significantly less mobile than controls during the intoxication period possibly due to a lower health condition, whereas they showed a greater mobility during the depuration period that might be related to an acute foraging for food. During depuration, MC elimination was total in gills and kidney, but partial in liver and muscle. Our results assess the MC transfer from gastropods to fish and the potential risk induced by bound MCs in the food web.

The role of neurotransmitter systems separate the hemispheres of the brain in action the new antiepileptic compounds AGB-31

Compound AGB-31, a monocarbamate derivative, is shown to possess a high antiepileptic activity. The mechanisms of antiepileptic action are connected with significant increase in glutamic acid decarboxylase activity in the left hemisphere of the brain, with trend of the glutamate content decrease in the left hemisphere and the tendency to increase GABA in both hemispheres. AGB-31 significantly (more than 3-fold) increases syntase nitric oxide activity in the left hemisphere and has a tendency to reduce the NO content in both hemispheres. AGB-31 significantly (by 63.4%), reduced glutathione peroxydase activity in the right hemisphere without changing it in the left, with a tendency to increase the activity of glutathione reductase in both hemispheres.

Effects of zearalenone on oxidative stress and inflammation in weanling piglets

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by the fungi of Fusarium genera. Piglets were fed for 18 days with a control or a ZEN (316 ppb) contaminated diet. At the end of the experiment tissue samples were taken for assessment of: lymphocyte proliferation, monocytes and granulocytes respiratory burst, inflammatory cytokine synthesis in blood and liver, expression of genes involved in oxidative stress or in inflammation, plasma biochemical parameters, total antioxidant status and nitric oxide synthesis. In blood, ZEN increases the respiratory burst of monocytes and the inflammatory cytokine (TNF alpha, IL-1 beta, IFN gamma) synthesis, while in liver, ZEN decreases the synthesis of all inflammatory cytokines investigated. In liver and spleen, different effect on the expression of genes involved in oxidative stress and inflammation was observed. While in liver, ZEN decrease the expression of cyclooxigenase gene, but increase the expression of glutathione peroxydase and catalase genes; in spleen, ZEN induces a decrease of the superoxide dismutase gene expression together with an increase of the cyclooxigenase. In conclusion, our results showed that liver, spleen and blood may also be target tissues in weanling piglets fed ZEN contaminated diet, with different effects on oxidative stress and inflammation.