Se-dependent Glutathione Peroxidase Research Articles

Mannose coated selenium nanoparticles normalize intestinal homeostasis in mice and mitigate colitis by inhibiting NF-κB activation and enhancing glutathione peroxidase expression

Impaired intestinal homeostasis is a major pathological feature of inflammatory bowel diseases (IBD). Mannose and selenium (Se) both demonstrate potential anti-inflammatory and anti-oxidative properties. However, most lectin receptors bind free monosaccharide ligands with relatively low affinity and most Se species induce side effects beyond a very narrow range of dosage. This has contributed to a poorly explored therapies for IBD that combine mannose and Se to target intestinal epithelial cells (IECs) for normalization gut homeostasis. Herein, a facile and safe strategy for ulcerative colitis (UC) treatment was developed using optimized, mannose-functionalized Se nanoparticles (M-SeNPs) encapsulated within a colon-targeted hydrogel delivery system containing alginate (SA) and chitosan (CS). This biocompatible nanosystem was efficiently taken up by IECs and led to increased expression of Se-dependent glutathione peroxidases (GPXs), thereby modulating IECs’ immune response. Using a mouse model of DSS-induced colitis, (CS/SA)-embedding M-SeNPs (C/S-MSe) were found to mitigate oxidative stress and inflammation through the inhibition of the NF-kB pathway in the colon. This stabilized mucosal homeostasis of IECs and ameliorated colitis-related symptoms, thereby providing a potential new approach for treatment of IBD.

AGE-RELATED CHARACTERISTICS OF GLUTATHIONE-DEPENDENT ENZYMES FUNCTIONING IN RATS UNDER CONDITIONS OF TOXIC INJURY BY ACETAMINOPHEN

Aim. The study is dedicated to evaluating the enzymatic activities of the glutathione system in liver cells of rats from different age groups under conditions of toxic injury caused by acetaminophen. In the experiments, rats of two age categories were used: young (138–150 days) and mature age (348–360 days). Mehods. Acute toxic injury from acetaminophen was induced by administering it per os at a dose of 1250 mg/kg of animal body weight during the last two days of the experiment. Results. Under conditions of simulated acute toxic injury by the medicinal xenobiotic acetaminophen in the livers of young and mature rats, a decrease was observed in glutathione-S-transferase, Se-dependent glutathione peroxidase, and glutathione reductase activities. A significant decrease in non-Se-glutathione peroxidase in liver cells is observed only in mature animals that were administered toxic doses of acetaminophen. The influence of the age component can be considered as one of the critically important factors in suppressing the functional activity of the glutathione-dependent enzymatic system, manifested by decreased activity of glutathione-S-transferase, non-Se-glutathione peroxidase, Se-dependent glutathione peroxidase and glutathione reductase under conditions of toxic injury caused by the medicinal xenobiotic acetaminophen. A more pronounced decrease in glutathione-dependent enzymes under conditions of acetaminophen intoxication is observed in animals aged 360 days. Cunclusion. The consequence of the established changes could be the disruption of acetaminophen biotransformation in Phase II involving the glutathione system, which can be considered as one of the risk factors for the development of drug-induced hepatotoxicity in different age groups.

Comparative Effects of Inorganic and Organic Dietary Sources of Selenium on Selenium Levels and Selenium-Dependent Glutathione Peroxidase Activity in Blood of Young Turkeys

The effect of various dietary sources of Se on Se-dependent glutathione peroxidase (SeGSH-Px) activity in plasma and whole blood was studied in turkeys. Dayold poults were fed low Se diets (supplemented with vitamin E) for 15 to 24 days before being fed experimental diets for 7 to 10 days. Menhaden fish meal (0.1 ppm Se) increased plasma SeGSH-Px activity by 45% of the response to 0.1 ppm Se as Na2SeO3. Poults supplemented with 0, 0.1, 0.2, or 0.4 ppm Se as Na2SeO3, had similar increases in plasma and whole blood Se levels; however, SeGSH-Px activity of plasma (r = 0.96) was better correlated with dietary Se than that of whole blood (r = 0.64). The supplement of 0.4 ppm Se increased the activity of SeGSH-Px almost 20 times in plasma but only 1.6 times in whole blood. The effectiveness of several compounds providing 0.2 ppm Se for increasing plasma SeGSH-Px activity was: Na2SeO4 > Se-dl-cystine > Se-dl-methionine and Se-dl-ethionine. The effect of Na2SeO3 was not significantly different from that of Se-dl-cystine, Se-dl-methionine or Se-dl-ethionine. The ratio of SeGSH-Px activity:Se concentration, indicating the amount of Se associated with enzyme activity, was highest in plasma of poults fed Na2SeO4 andSe-dl-cystine. The data demonstrate differences in the availability of various Se sources for SeGSH-Px activity in poults.selenium glutathione peroxidase turkeys fish meal

Oxidative Stress May Contribute to the Intestinal Dysfunction of Weanling Rats Fed a Low Protein Diet

Intestinal function is impaired in malnutrition. Because oxidative stress is a component of gastrointestinal injury, and malnutrition may reduce antioxidant defenses, we investigated the involvement of oxidative stress in the intestinal dysfunction due to malnutrition. Weanling rats were fed either a normal protein (22% casein) or a low protein (6% casein) diet for 4 wk. In intestinal homogenates, we assessed free radical damage and enzymatic antioxidant defenses. In jejunal fragments mounted in Ussing chambers, we measured ionic transport by short-circuit current (Isc) and protein permeability by transepithelial fluxes of beta-lactoglobulin. Catalase activity and the thiobarbituric acid-reacting substances concentration were greater in intestinal mucosa of the low protein group, whereas the glutathione concentration and the activities of superoxide dismutase and Se-dependent glutathione peroxidase were the same as in the normal protein group intestinal mucosa. Both basal Isc and the delta Isc induced by glucose and forskolin, as well as beta-lactoglobulin fluxes, were higher in the low protein group. Exogenous H2O2 stress increased Isc significantly more in the low protein than the normal protein group but did not alter protein permeability. These results show that malnutrition induces both intestinal free radical damage and altered epithelial transport, suggesting that oxidative stress may contribute to the intestinal dysfunction associated with malnutrition.

The Correlation between Selenium-Dependent Glutathione Peroxidase Activity and Oxidant/Antioxidant Balance in Sera of Diabetic Patients with Nephropathy.

Oxidative stress is an imbalance between free radical's production and the body's ability to counteract or detoxify their harmful effects through neutralization by antioxidants, oxidative stress is thought to be involved in the pathogenesis of diabetic nephropathy. One of the key enzymatic antioxidants is glutathione peroxidase (GPx), which plays an important protective function in diabetes complications, by reducing the rising state of oxidative stress and removing toxicity from peroxides and converting them into a non-toxic substance. The objective of this research was to evaluate the rule of glutathione peroxidase in regulate oxidants/antioxidants levels diabetic patients with nephropathy. In a case-control study, we assessed serum GPx activity (Se-Dependent, non-selenium dependent and total GPx), total oxidant, lipid peroxidation, total antioxidant, and catalase in healthy control subjects (group 1), in diabetic patients without diabetic nephropathy (group 2) and diabetic patients with nephropathy (group 3). GPx activity was significantly lower in T2D patients with and without nephropathy compared to healthy subject's control. Total oxidants and lipids peroxidation have a negative correlation with the GPx and other antioxidants. Decreased GPx activity indicate a relationship between GPx activity and diabetic nephropathy.

Antioxidant Defense in the Hepatopancreas and Nerve Ganglia of the Mollusk Lymnaea stagnalis after Acute Experimental Hyperglycemia

The state of the antioxidative defense system in the hepatopancreas and central nerve ganglia was investigated in the mollusk Lymnaea stagnalis in the normal conditions and one day after acute experimental hyperglycemia induced by a 2-h incubation in 100 mM glucose solution. It was established that hyperglycemic exposure caused a 1.6- and 1.5-fold increase in the reduced glutathione (GSH) level and superoxide dismutase (SOD) activity, respectively, as observed against the background of a 1.3-fold decrease in the total protein level. At the same time, activity of Se-dependent glutathione peroxidase (Se-GP) and the level of TBA reactive substances (TBARS) remained intact. Hepatopancreatic tissues were characterized by a 1.3-fold decrease in TBARS, as detected against the background of a 1.1-fold increase in the total protein level, while other antioxidative defense components (SOD, GSH, Se-GP) remained invariable. It is assumed that the more developed antioxidative system in central ganglia is essential for providing sustained functioning of nerve cells in L. stagnalis under dramatic disturbances of glucose homeostasis in the internal environment.

Surplus of dietary micronutrients promotes antioxidant defense and improves fin erosions in European seabass (Dicentrarchus labrax) fry

Dietary micronutrient supplementation can serve as skin health promotor to prevent from natural infections and can be applied to decrease the use of antibacterial agents and their impact on the environment. Such supplementation has indicated anti-inflammatory and antioxidant properties in farmed fish. In this study, dietary supplementation of zinc, selenium, ascorbic acid and niacin, at levels 2 to 3-fold higher than recommended, was evaluated as a measure to promote skin health and antioxidant defense in European seabass, Dicentrarchus labrax, fry. For this purpose, fish survival, growth performance, fin and skin erosions as well as whole-fish antioxidant enzyme activity (catalase, selenium (Se)-independent and dependent glutathione peroxidase) were assessed. Moreover, bacterial load in the rearing water and skin mucus were evaluated to assess the potential of the dietary micronutrient mixture as a preventive from natural infections. A group fed with a diet including these micronutrients at recommended levels served as a control. Surplus of these micronutrients significantly reduced the percentage of fish with eroded fins, while also induced the activity of catalase and Se-dependent glutathione peroxidase. Fish growth and bacterial loads in the water and fish skin mucus were not affected, whereas no skin lesions were observed. Overall, a mineral- and vitamin-supplemented diet at levels higher than recommended seems to act as a promotor of skin health and prevent from fin erosions, potentially through an increase in the antioxidant defense system.

Ovarian stimulated cycles reduce protection of follicular fluid against free radicals

Controlled ovarian hyperstimulation cycle with exogenous gonadotropins (COH) is associated with clinical complications. The aim of this work was to determine whether COH alters the physiological antioxidant status of follicular fluid in women with no reproductive dysfunction, compared to the natural cycle (NC). In this longitudinal study, forty-one women (oocyte donors) consecutively underwent NC and COH. Follicular fluid was collected at oocyte retrieval and different redox biomarkers were determined: total antioxidant activity (TAA), oxygen radical absorbance capacity (ORAC), nitric oxide, α- and γ-tocopherol, the fatty acid composition, activities of superoxide dismutase, catalase, total and Se-dependent glutathione peroxidases, and the antioxidant paraoxonase (PON) family. Results showed that TAA (1.70 ± 0.03 mM versus 1.86 ± 0.03 mM, p < 0.05), α-tocopherol (4.37 ± 0.26 μM versus 5.74 ± 0.30 μM, p < 0.05), PON1 paraoxonase (245 ± 24 nmol/min/ml versus 272 ± 27 nmol/min/ml, p < 0.05), PON1 arylesterase (87.2 ± 4.6 μmol/min/ml versus 99.3 ± 4.8 μmol/min/ml, p < 0.05), and PON3 simvastatinase (13.48 ± 0.52 nmol/min/ml versus 16.29 ± 0.72 nmol/min/ml, p < 0.001) were significantly lower in COH versus NC. Fatty acids from COH were more saturated, increasing palmitate and decreasing the n-6 and total polyunsaturated fatty acids (PUFAs). Docosahexaenoic acid also increased (p < 0.05). Results suggest that COH could lead to premature ovarian aging and provide new insights into the possible prevention of the adverse effects of ovarian hyperstimulation by directing therapeutic applications to the maintenance of the redox balance and fatty acid status, with special attention to paraoxonase proteins and docosahexaenoic acid.

Abstract 881: A role for microsomal glutathione transferase 1 in melanin biosynthesis in melanoma

Abstract Higher organisms have multiple defenses against toxic chemical insult, ultraviolet light (UVR) and oxidative stress. These include thioredoxin and glutathione dependent enzymes, some of which are selenium (Se) dependent, including thioredoxin reductases, Se-dependent glutathione peroxidases, Se-independent glutathione transferases and peroxiredoxins. Microsomal glutathione transferase 1 (MGST1) shares an important and unique characteristic with Se-dependent glutathione peroxidase GPX4, namely the ability to reduce lipid hydroperoxides directly in membranes. In contrast to most other glutathione transferases and peroxidases, we previously found that deletion of MGST1 in mice was embryonic lethal, signifying some essential functional importance. We found that MGST1 was crucial for embryonic development through regulating early hematopoiesis in both zebrafish and mouse derived hematopoietic stem cells. Interestingly, after partial knock-down MGST1, the number of melanocytes located at the midline of zebrafish embryos was significantly reduced. Melanocytes are specialized cells that produce melanin, contributing to skin color, but also providing an antioxidant defense system that includes UVR - causative in the initiation of melanoma. Both mRNA and protein levels of MGST1 were markedly decreased in several amelanotic melanoma cell lines and melanogenesis was significantly decreased in B16 melanoma cells when MGST1 expression was knocked down by 60%. This was accompanied by increased UVB-induced cell death in these B16 cells. In contrast, in normal human melanocytes, recombinant adenovirus induced over-expression of MGST1 induced melanogenesis, concomitant with an increase of tyrosinase protein levels. UVB light was used to show that stimulus of melanin biosynthesis occurred in different melanoma cells in quantitative agreement with their levels of MGST1. We conclude that within the melanin synthetic pathway, MGST1 is critical in regulating conversion of dopaquinone to glutathionyl-DOPA, a precursor of pheomelanin. In the absence of MGST1, dopaquinone can cause toxicities and result in reduced or absent levels of melanin, leading to a deficiency in protection against UVR-induced DNA damage. Thus, absence of MGST1 produces embryonic lethality and influences the susceptibility of skin melanocytes to melanoma. Citation Format: Jie Zhang, Zhi-wei Ye, Danyelle M. Townsend, Ralf Morgenstern, Kenneth D. Tew. A role for microsomal glutathione transferase 1 in melanin biosynthesis in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 881.

Altered dietary selenium influences brain iron content and behavioural outcomes

Selenium (Se) is an essential micronutrient that provides antioxidant defence through selenoproteins, but at high concentrations, deleterious effects have been reported. The present study examines the antioxidant response in brain regions and behavioural functions in mice under various dietary Se paradigms; Se-deficient, Se-adequate and Se-excess. Se levels were found to be reduced in the cortex and hippocampus of Se-deficient animals, whereas no change was observed in animals on Se-excess diet. In the hippocampus, iron (Fe) levels increased in animals on Se-deficient and Se-excess diets. Moreover, in Se-deficient animals, Fe levels increased in cortex also. Interestingly, Se content in the hair positively correlated with the dietary Se intake. Total and Se-dependent glutathione peroxidase activity decreased in the cortex, hippocampus and cerebellum of animals on Se-deficient diet. On the other hand, the activity of these enzymes decreased in the cortex of animals on Se-excess diet. Further, lipid peroxidation increased in the cortex of animals on Se-deficient diet and in the hippocampus of animals on Se-excess diet. Cognitive functions assessed by Morris water maze and Y-maze tests revealed deficits in Se-deficient state. However, in Se-excess state cognitive deficits were observed only in Y-maze test. These findings suggest that long-term dietary variation in Se influences oxidative stress that impacts cognitive functions. Therefore, it is suggested that maintenance of Se status during postnatal development may be crucial for mental health.

Environmental mercury exposure and selenium-associated biomarkers of antioxidant status at molecular and biochemical level. A short-term intervention study

Mercury (Hg) is a potent toxicant. In the field of public health a chronic-low-level environmental Hg exposure resulting from fish consumption in general population is still being discussed. The objective of the study was to assess the influence of real Hg exposure on biomarkers of selenium (Se) status and selected biomarkers of pro-oxidant/anti-oxidant effects in healthy men (n = 67) who participated in the short-term intervention study consisting in daily fish consumption for two weeks. The analysis included Se level, Se-associated antioxidants at molecular (profile of 7 genes encoding selected proteins related to antioxidant defense) and biochemical levels (Se-dependent glutathione peroxidases activities and plasma selenoprotein P concentration). A pro-oxidant/anti-oxidant balance was explored using a biomarker of plasma lipid peroxidation and total antioxidant activity. The study revealed significant correlations (p < 0.05) between the biomarkers of exposure to Hg, Se level and Se-dependent antioxidants. Even though the risk of adverse effects of Hg for volunteers was substantially low, biomarkers of Hg altered levels of circulation selenoproteins and their genes expression. Changes in genes expression during study differed between the main enzymes involved in two systems: downregulation of thioredoxin reductase1 and upregulation of glutathione peroxidases. Hg exposure caused imbalance between the biomarkers of pro-oxidant/anti-oxidant effects.

Effects of oral selenium and magnesium co-supplementation on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in rats fed a high-fat diet

BackgroundSupplementation with Selenium (Se) has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, in combination with supplemental magnesium, on high fat-induced hyperlipidemia have not been studied. This study was designed to elucidate the effects of oral selenium and magnesium co-supplementation on antihyperlipidemic and hepatoprotective, antioxidative activities, and related gene expression in a hyperlipidemic rat model.MethodsForty male Sprague Dawley rats were divided into 4 groups: one group served as control group (CT), provided control diet; The other groups were made hyperlipidemic with high-fat diet; specifically, a high-fat diet group (HF); low-dose selenium (0.05 mg/kg·bw) + low-dose magnesium (5.83 mg/kg·bw) supplement high-fat diet group (HF + LSe + LMg) and high-dose selenium (0.10 mg/kg·bw) + high-dose magnesium (58.33 mg/kg·bw) supplement high-fat diet group (HF + HSe + HMg). The first 4 weeks of the experiment was a hyperlipidemia inducing period using high-fat diet and the following 8 weeks involved in selenium and magnesium co-supplementation. On day 0, 20, 40 and 60 of the intervention, lipid profile was measured. At the end of the 12-week experiments, final blood and liver samples were collected for the measurements of lipid profile, antioxidative indexes, pathological examination, and liver lipid metabolism related gene expression.ResultsThe elevated levels of serum and liver total cholesterol (TC) and serum LDL-C induced by feeding high-fat diets were significantly reduced by low-dose Se and Mg co-supplementation. Both doses of selenium and magnesium co-supplementation notably decreased the blood and liver TG levels, liver function indexes ALT and AST and the ratio of TC/HDL-C and TG/HDL-C. In contrast, Se and Mg supplementation showed a substantial increase in Se-dependent glutathione peroxidase (GSH-Px) and SOD activities and an significant reduce of level of MDA of hyperlipidemic rats. Oil Red O staining showed that selenium and magnesium co-supplementation significantly reduced hepatic intracellular triacylglycerol accumulation. H&E staining also showed that selenium and magnesium co-supplementation can attenuate liver steatosis. Selenium and magnesium co-supplementation remarkably inhibited the mRNA expression level of hepatic lipogenesis genes liver X receptor alpha (LXRα),SREBP-1c and FASN (fatty acid synthase), regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1) and lecithin cholesterol acyltransferase (LCAT) in the liver of hyperlipidemia rats.ConclusionsOral selenium and magnesium co-supplementation inhibited an increase of lipid and liver profile and liver function index induced by a high-fat diet, and enhanced the activity of the antioxidant enzymes. Selenium combined with magnesium is a promising therapeutic strategy with lipid-lowering and antioxidative effects that protects the liver against hyperlipidemia.

P-59 - Antioxidant status of human follicular fluid: natural versus controlled ovarian hyper-stimulated cycles

Controlled ovarian hyperstimulation (COH) is used in standard protocols in in vitro fertilization (IVF). However, its use is associated with clinical complications such as ovarian hyperstimulation syndrome. The evidence indicates that the natural cycle (NC) has a lower risk and is more physiological. In this study, we have determined the antioxidant status of follicular fluid at the time of oocyte retrieval following NC or COH. Forty-one fertile women (oocyte donors) followed both cycles. In NC no exogenous gonadotrophins were used, and only hCG was given to induce ovulation. We determined TAA, ORAC, - and tocopherol, nitric oxide, and the activities of SOD, catalase, total and Se-dependent glutathione peroxidases, and paraoxonases. Results showed that TAA, -tocopherol, and the paraoxonase, arylesterase, and simvastatinase activities were significantly higher in NC, compared with COH. Our results indicate that NC is associated with higher follicle antioxidant protection and provide important insights into prevention of hyperstimulation side effects.

Antioxidant enzymes activities in the liver of sea bass, Dicentrarchus labrax, juveniles fed diets with different levels of vitamins

Antioxidant enzymes activities in the liver of sea bass, Dicentrarchus labrax, juveniles fed diets with different levels of vitamins

Selenium-Dependent Glutathione Peroxidases During Tumor Development.

Five out of eight human glutathione peroxidases (GPxes) are selenoproteins and thus their expression depends on the selenium (Se) supply. Most Se-dependent GPxes are downregulated in tumor cells, while only GPx2 is considerably upregulated. Whether expression profiles of GPxes predict tumor development and patient survival is controversially discussed. Also, results from in vitro and in vivo studies modulating the expression of GPx isoforms provide evidence for both anti- and procarcinogenic mechanisms. GPxes are able to reduce hydroperoxides, which otherwise would damage DNA, possibly resulting in DNA mutations, modulate redox-sensitive signaling pathways affecting proliferation, differentiation, and cellular metabolism or initiate cell death. Considering these different processes, the role and functions of individual Se-dependent GPx isoforms will be discussed herein in the context of tumorigenesis.

Toxic effects of copper oxide nanoparticles in midgut and fat body of Galleria mellonella (Lepidoptera: Pyralidae)

In recent years, Cd-based quantum dots (QDs) have generated interest from the life sciences community due to their potential applications in nanomedicine, biology and electronics. However, these engineered nanomaterials can be released into the marine environment, where their environmental health hazards remain unclear. This study investigated the tissue-specific responses related to alterations in the antioxidant defense system induced by CdTe QDs, in comparison with its dissolved counterpart, using the marine mussel Mytilus galloprovincialis. Mussels were exposed to CdTe QDs and dissolved Cd for 14 days at 10 μgCd L−1 and biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (total, Se-independent and Se-dependent GPx) and glutathione-S-transferase (GST) activities] were analyzed along with Cd accumulation in the gills and digestive gland of mussels. Results show that both Cd forms changed mussels’ antioxidant responses with distinct modes of action (MoA). There were tissue- and time-dependent differences in the biochemical responses to each Cd form, wherein QDs are more pro-oxidant when compared to dissolved Cd. The gills are the main tissue affected by QDs, with effects related to the increase of SOD, GST and GPx activities, while those of dissolved Cd was associated to the increase of CAT activity, Cd accumulation and exposure time. Digestive gland is a main tissue for accumulation of both Cd forms, but changes in antioxidant enzyme activities are smaller than in gills. A multivariate analysis revealed that the antioxidant patterns are tissue dependent, indicating nano-specific effects possibly associated to oxidative stress and changes in redox homeostasis.

Dual behavior of N-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains

Objectives: Ethanol (EtOH) causes oxidative stress in embryos. Because N-acetylcysteine (NAC) failures and successes in ameliorating EtOH-induced oxidative stress have been reported, the objective was to determine if exogenous NAC ameliorated EtOH-induced oxidative stress within embryonic chick brains.Methods: Control eggs were injected with approximately 25 µl of water on day 0, 1, and 2 of development (E0–2). Experimental eggs were injected with dosages of either 3.0 mmol EtOH/kg egg; 747 µmol NAC/kg egg; 3.0 mmol EtOH and 747 µmol NAC/kg egg; 1000 µmol NAC/kg egg; or 3.0 mmol EtOH and 1000 µmol NAC/kg during the first 3 days of development (E0–2). At 11 days of development (E11; late embryogenesis), brains were harvested and subsequently assayed for oxidative stress markers including the loss of long-chain membrane polyunsaturated fatty acids (PUFAs); the accumulation of lipid hydroperoxides (LPO); decreased glutathione (GSH) and glutathione/glutathione disulfide (GSSG) levels; and decreased glutathione peroxidase (GPx) activities.Results: EtOH (3 mmol/kg egg), medium NAC (747 µmol/kg egg), and EtOH and medium NAC promoted oxidative stress. These treatments caused decreased brain membrane long-chain PUFAs; increased LPO levels; decreased GSH levels and GSH/GSSG levels; and decreased Se-dependent GPx activities. High NAC dosages (1000 µmol/kg egg) attenuated EtOH-induced oxidative stress within EtOH and high NAC-treated chick brains.Discussion: Exogenous EtOH and/or medium NAC propagated oxidative stress. Meanwhile, high NAC ameliorated EtOH-induced oxidative stress.

The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels.

Inhibition of Ca2+ entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca2+-permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca2+ concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress, although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in hippocampus. SCOP can result in augmented ROS release in hippocampal neurons, leading to Ca2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca2+ provided that intracellular Ca2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1 channel activation through the modulation of aging oxidative reactions and Se-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Responses in Micro-Mineral Metabolism in Rainbow Trout to Change in Dietary Ingredient Composition and Inclusion of a Micro-Mineral Premix.

Responses in micro-mineral metabolism to changes in dietary ingredient composition and inclusion of a micro-mineral premix (Fe, Cu, Mn, Zn and Se) were studied in rainbow trout. In a 2 x 2 factorial design, triplicate groups of rainbow trout (initial weight: 20g) were fed over 12 weeks at 17°C a fishmeal-based diet (M) or a plant-ingredient based diet (V), with or without inclusion of a mineral premix. Trout fed the V vs. M diet had lower feed intake, growth, hepato-somatic index, apparent availability coefficient (AAC) of Fe, Cu, Mn and Zn and also lower whole body Se and Zn concentration, whereas whole body Fe and Cu and plasma Fe concentrations were higher. Feeding the V diet increased intestinal ferric reductase activity; at transcriptional level, hepatic hepcidin expression was down-regulated and ferroportin 1 was up-regulated. Transcription of intestinal Cu-transporting ATPases and hepatic copper transporter1 were higher in V0 compared to other groups. Among the hepatic metalo-enzyme activities assayed, only Se-dependent glutathione peroxidase was affected, being lower in V fed fish. Premix inclusion reduced the AAC of Fe, Cu and Zn; increased the whole body concentration of all micro- minerals; up-regulated hepatic hepcidin and down-regulated intestinal ferroportin 1 transcription; and reduced the transcription of Cu-transporting ATPases in the intestine. Overall, the regulation of micro-mineral metabolism in rainbow trout, especially Fe and Cu, was affected both by a change in ingredient composition and micro-mineral premix inclusion.

The importance of pyridoxine for the impact of the dietary selenium sources on redox balance, embryo development, and reproductive performance in gilts

This study aimed to determine the effects of dietary pyridoxine and selenium (Se) on embryo development, reproductive performance and redox system in gilts. Eighty-four gilts were fed one of five diets: CONT) basal diet; MSeB60) CONT+0.3mg/kg of Na-selenite; MSeB610) diet 2+10mg/kg of HCl-pyridoxine; OSeB60) CONT+0.3mg/kg of Se-enriched yeast; and OSeB610) diet 4+10mg/kg of HCl-pyridoxine. Blood samples were collected for long-term (each estrus and slaughter) and peri-estrus (fourth estrus d −4 to d +3) profiles. At slaughter (gestation d 30), organs and embryos were collected. For long-term and peri-estrus profiles, Se level and source affected (P<0.01) blood Se concentration whereas B6 level increased (P<0.01) erythrocyte pyridoxal-5-phosphate concentration. A B6 level (P<0.05) effect was observed on long-term plasma Se-dependent glutathione peroxidase (Se-GPX) activity whereas peri-estrus Se-GPX was minimum on d −1 (P<0.01). Selenium level increased sows’ organs and embryo Se concentration (P<0.01). Selenium source tended to enhance embryo Se content (P=0.06). Within-litter embryo Se content was increased by B6 level (P<0.01). Selenium level tended to affect Se-GPX and total GPX activities in organs mitochondria (P=0.09 and 0.07, respectively). Selenium source affected kidney ATP synthesis (P=0.05). In conclusion, B6 level affected the Se-GPX activity on a long-term basis, whereas the basal level of Se was adequate during the peri-estrus period. Embryo quality was not improved by dietary Se, and B6 impaired within-litter homogeneity.