Se-dependent Glutathione Peroxidase Activity Research Articles

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.

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.

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.

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.

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 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.

Supplementation with Selenium yeast on the prooxidant–antioxidant activities and anti-tumor effects in breast tumor xenograft-bearing mice

Selenium (Se) is essential for antioxidant activity involved in immune function and anti-carcinogenic action, whereas at higher concentrations, Se may have pro-oxidant properties. The present study was aimed at determining the effects of Se supplementation, as Se yeast, on oxidative stress in non-tumor/tumor tissues, as well as regulation of the apoptotic process, and immune responses in mice-bearing breast tumor xenografts. Female BALB/cByJNarl mice were divided into control (CNL and CNL-con), Se-supplemented control (CNL-HS, given as a single oral dose of 912 ng Se daily), breast tumor-bearing (TB and TB-con), TB-LS (228 ng Se), TB-MS (456 ng Se) and TB-HS (912 ng Se) groups. All mice were treated with/without Se for 14 days. A number of variables were further measured. Compared with the TB groups, tumor bearing mice with Se supplement had increased plasma Se concentrations, reduced erythrocyte Se-dependent glutathione peroxidase (GPx) activity and malondialdehyde (MDA) products and inhibited tumor growth. They have also higher Se concentrations in non-tumor and tumor tissues. Significantly elevated concentrations of MDA and reduced GPx activities, as well as increased anti-apoptotic bcl-2 and tumor suppressor p53 concentrations in tumor tissues were observed as Se accumulated in tumor, whereas lower MDA products were found in various non-tumor tissues than did the corresponding values. Further, there were elevated concentrations of Th1-derived cytokines and decreased Th2-type interleukin (IL)-4 in tumor-bearing mice with the treatment of Se. In conclusion, accumulation of Se in tumors may induce oxidative stress and p53-dependent pro-oxidative apoptosis, thus inhibiting the growth of breast tumor.

Influence of the forms and levels of dietary selenium on antioxidant status and oxidative stress-related parameters in rainbow trout (Oncorhynchus mykiss) fry

Se is an essential micronutrient required for normal growth, development and antioxidant defence. The objective of the present study was to assess the impact of dietary Se sources and levels on the antioxidant status of rainbow trout (Oncorhynchus mykiss) fry. First-feeding fry (initial body weight: 91mg) were fed either a plant- or fishmeal-based diet containing 0·5 or 1·2mg Se/kg diet supplemented or not with 0·3mg Se/kg diet supplied as Se-enriched yeast or sodium selenite for 12 weeks at 17°C. Growth and survival of rainbow trout fry were not significantly affected by dietary Se sources and levels. Whole-body Se was raised by both Se sources and to a greater extent by Se-yeast. The reduced:oxidised glutathione ratio was raised by Se-yeast, whereas other lipid peroxidation markers were not affected by dietary Se. Whole-body Se-dependent glutathione peroxidase (GPX) activity was enhanced in fish fed Se-yeast compared to fish fed sodium selenite or non-supplemented diets. Activity and gene expression of this enzyme as well as gene expression of selenoprotein P (SelP) were reduced in fish fed the non-supplemented plant-based diet. Catalase, glutamate-cysteine ligase and nuclear factor-erythroid 2-related factor 2 (Nrf2) gene expressions were reduced by Se-yeast. These results suggest the necessity to supplement plant-based diets with Se for rainbow trout fry, and highlight the superiority of organic form of Se to fulfil the dietary Se requirement and sustain the antioxidant status of fish. GPX and SelP expression proved to be good markers of Se status in fish.

Dose-dependent protective effects of dietary selenium on abaloneHaliotis discus hannaiIno against the toxicity of waterborne copper

This study was designed to assess the protective effects of dietary selenium (Se) on abalone Haliotis discus hannai Ino against the toxicity of waterborne copper (Cu). A 60-day feeding trial was conducted in a static water system for abalone (initial weight: 3.17 ± 0.01 g) exposed to 0.02 mg L−1 of waterborne Cu. The animals were fed one of the three experimental diets with 0.10, 1.31 and 4.20 mg kg−1 of Se from Na2SeO3·5H2O respectively. Results showed that the abalone fed 1.31 mg kg−1 of dietary Se had the lowest Cu concentration in shell, muscle, mantle, gill, hepatopancreas and serum. Meanwhile, the significant lowest contents of malondiadehyde and protein carbonyl in hepatopancreas were also found in the treatment with 1.31 mg kg−1 of dietary Se (P < 0.05). In addition, this treatment had significant higher glutathione content and thioredoxin reductase activity in hepatopancreas (P < 0.05). However, the activity of Se-dependent glutathione peroxidase (Se-GPx) was significantly decreased in the treatment with 4.20 mg kg−1 of dietary Se (P < 0.05). In this treatment, the protein carbonyl content in hepatopancreas was significantly higher than that in the group with 1.31 mg kg−1 of dietary Se (P < 0.05). In conclusion, in terms of anti-oxidation and Cu accumulation, the protective effects of dietary Se on abalone against waterborne Cu were dose-dependent. The 1.31 mg kg−1 of dietary Se had this effect, but not 4.20 mg kg−1 of dietary Se. Moreover, the latter increased the oxidative stress in abalone exposed to the waterborne Cu.

Caloric Restriction Diet Induces Specific Epigenotypes Associated with Life Span Extension

The lifespan of Wistar rats on caloric restriction diet (CRD) is correlated with the changes in prooxidant-antioxidant balance, in the contents of triiodothyronine, and thyroxin (epigenotype characteristics). It has been shown that in a month after the moment of one-month-old rats began to receive CRD the part (up to 15 %) of experimental animals died without any apparent cause, irrespective of the degree of calorie restriction (40 %, 57 % and 60 % weight-loss). The rest of animals with 40 %, 57 % and 60 % weight-loss had longer life span in comparison with control group. The CRD-induced life-span prolongation in animals was accompanied by the induction of specific epigenotypes featured by acceleration of the electron transfer rate in electron transport chain and subsequent reduced production of reactive oxygen species and increased antioxidant activity. The activity of glutathione reductase, glutathione transferase, NADH-cytochrome C reductase, isocitrate dehydrogenase was elevated. The activity of Se-dependent glutathione peroxidase was higher more than 30 times as compared with control. Likewise, the epigenotypes of animals with 40 %, 57 % and 60 % weight-loss CR, were characterized by 37, 43 and 56 % decrease in triiodothyronine and 50, 25, 39 % decrease in tyrosine, respectively. The observed induction of specific epigenotypes is associated with higher life-span and is related to the multivariant metabolic strategies of adaptation to CRD.

Distribution of Selenium and Oxidative Stress in Breast Tumor-Bearing Mice

The present study investigated the effects of breast tumors on the blood and tissue distribution of essential trace mineral selenium (Se), and oxidative stress status of mice. Female 10-week-old BALB/cByJNarl mice were randomly assigned into control (CNL) and breast tumor-bearing (TB) groups. TB mice were injected subcutaneously into the right hind thigh with 5 × 106 EMT6 mouse mammary tumor cells. After 22 days, we measured Se concentrations, Se-dependent glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) products (indicator of oxidative stress) in plasma, various tissues, and plasma vascular endothelial growth factor (VEGF) concentrations. There were no significant differences in body weights and daily intake between both groups. Compared with the CNL group, TB mice have decreases in plasma Se concentrations and GPx activities, as well as higher plasma VEGF and MDA concentrations. Plasma Se concentrations were also negatively correlated with plasma MDA and VEGF concentrations. Furthermore, tissue Se concentrations and GPx activities in TB animals were lower; whereas the MDA concentrations higher in various tissues including liver, kidney, brain, lung, spleen, and thymic tissues. In conclusion, disruption of Se homeostasis critically reflects oxidative stress in target tissues, thus may increase the risk for progression of breast cancer and metastasis.

Dietary Selenium as a Modulator of PCB 126–Induced Hepatotoxicity in Male Sprague-Dawley Rats

Homeostasis of selenium (Se), a critical antioxidant incorporated into amino acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR) agonists. Here we examined the importance of dietary Se in preventing the toxicity of the most toxic polychlorinated biphenyl congener, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and 2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 μmol/kg body weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose-dependent increases in liver weight and at the highest PCB 126 dose decreases in whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was significantly increased even at the lowest dose of PCB 126, indicating potent AhR activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner, and this was accompanied by diminished Se-dependent glutathione peroxidase activity. Both these effects were partially mitigated by Se supplementation. Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state, although significantly diminished in the lowest dietary Se groups, were not affected by PCB exposure. In addition, PCB 126-induced changes in hepatic copper, iron, manganese, and zinc were observed. These results demonstrate that supplemental dietary Se was not able to completely prevent the toxicity caused by PCB 126 but was able to increase moderately the levels of several key antioxidants, thereby maintaining them roughly at normal levels.

Selenium concentrations and enzyme activities of glutathione metabolism in wild long‐tailed ducks and common eiders

The relationships of selenium (Se) concentrations in whole blood with plasma activities of total glutathione peroxidase, Se-dependent glutathione peroxidase, and glutathione reductase were studied in long-tailed ducks (Clangula hyemalis) and common eiders (Somateria mollissima) sampled along the Beaufort Sea coast of Alaska, USA. Blood Se concentrations were >8 µg/g wet weight in both species. Linear regression revealed that the activities of total and Se-dependent glutathione peroxidase were significantly related to Se concentrations only in long-tailed ducks, raising the possibility that these birds were experiencing early oxidative stress.

Dietary selenium requirement for juvenile cobia, Rachycentron canadum L.

A 10-week feeding trial was conducted to estimate the optimum dietary selenium (Se) requirement for juvenile cobia, Rachycentron canadum L. The basal diet was formulated to contain 50.6% crude protein from vitamin-free casein, gelatin. A control diet (no added seleno-dl-methionine) and five experimental diets containing 0.20, 0.40, 0.60, 0.80 and 1.00 mg seleno-dl-methionine kg−1 were prepared. Each diet was randomly fed to triplicate groups of juvenile cobia with initial weight 6.27±0.03 g in a flow-through system. The Se concentration in rearing water was monitored during the feeding period, and was not detectable. The dietary Se level significantly influenced the survival, specific growth rate (SGR), feed efficiency and the Se concentrations in the whole body and vertebra of cobia. The Se-dependent glutathione peroxidase (EC 1.11.119) activity increased with an increase in the dietary Se levels (P<0.05). Hepatic glutathione reductase (EC 1.6.4.2) activity was the highest in fish fed the diet with 0.21 mg Se kg−1, and declined with an increase in the dietary Se levels. Based on broke-line regression of SGR, the Se concentration in the whole body and vertebra, the Se requirements of juvenile cobia were 0.788, 0.811 and 0.793 mg Se kg−1 diet in the form of seleno-dl-methionine respectively.

Selenium Supplementation Decreases Hepatic Fibrosis in Mice After Chronic Carbon Tetrachloride Administration

Oxidative stress stimulates fibrogenesis, and selenium (Se) has antioxidant properties. This study determined whether Se supplementation affects CCl(4)-induced liver injury and fibrosis. Mice were administered CCl(4) over 4 weeks, while controls received olive oil. Se was provided as sodium selenite in the drinking water. Se increased liver Se-dependent glutathione peroxidase activity and decreased liver malondialdehyde after CCl(4). Se decreased liver inflammation but not necrosis caused by CCl(4). Se increased hepatocyte apoptosis after CCl(4) and the pro-apoptotic BAX and Bcl Xs/l proteins. Stellate cell apoptosis occurred only after CCl(4) in Se-supplemented mice. Se decreased stellate cell number and fibrosis after CCl(4). Liver matrix metalloproteinase-9 increased after CCl(4) with Se supplementation. In conclusion, Se supplementation decreased hepatic fibrosis after CCl(4) in the setting of decreased inflammation but increased apoptosis. The principal mechanisms for the decreased fibrosis are a lower number of collagen-producing stellate cells and increased collagen degradation.

Lipid peroxidative stress and antioxidant defence status during ontogeny of rainbow trout (Oncorhynchus mykiss)

The objective of the present study was to characterise some important antioxidant enzymes and their relationships with retinoids and lipid peroxidation during rainbow trout (Oncorhynchus mykiss) early development. Eggs were incubated at 7 degrees C until the swim-up stage whereupon fry were fed two semi-purified diets with 0% (CO) and 8% (OX) oxidised lipid respectively for 2 months at 17 degrees C. The activities and gene expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were determined as well as the levels of retinoids, F2-isoprostanes and lipid-soluble fluorescent products (LSFP) at various developmental stages. Only SOD had a detectable activity in embryos which increased during development and was linked with an increase of mitochondrial (SOD2) and cytosolic (SOD1) gene expression. SOD1 and SOD2 mRNA were more abundant in fry fed OX than in fry fed CO. CAT activity and gene expression also increased during development and were higher in fry fed OX compared with fry fed CO. Activity of Se-dependent GPX (Se-GPX) increased during development. The gene expression of cytosolic Se-GPX (GPX1) increased from hatching to 2-month-fed fry. Both phospholipid-hydroperoxide GPX and GPX1 genes were more expressed in fry fed OX than in fry fed CO. Retinoids decreased during development and, by 2 months, were lowered in fry fed OX compared with those fed CO. The levels of LSFP were higher in fry fed OX compared with fry fed CO. The present study demonstrates that antioxidant defence systems are active all through the development of rainbow trout and modulated by feeding oxidised lipid.

Evaluation of sex specificity on oxidative stress induced in lungs of mice irradiated by 12C 6+ ions

The aim of this work is to identify if there is sex specificity on 12C 6+ ion-induced oxidative damage in mouse lung at different time points. Kun-Ming mice were divided into two groups, each composed of six males and six females: control group and irradiation group with a single acute dose of 4 Gy. Animals were sacrificed at 2, 4 and 12 h respectively, there lungs were removed immediately, and the oxidative stress-related biomarkers were measured by Diagnostic Reagent Kits. The results showed that the relative activities of superoxide dismutase (4 h), catalase (2 h) and Se-dependent glutathione peroxidase (12 h) have significant changes ( P<0.05) between male groups and female groups, suggesting that the lungs of male mice are more sensitive to counteracting the oxidative challenge. Moreover, higher levels of malondiadehyde and lower contents of glutathione were also found in males, indicating that oxidative stress induced by 12C 6+ ion is pronounced in the lungs of males. We thought that these sex-responded differences may be attributed to the influence of sex hormones.

Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in d-galactosamine-sensitized mice

d-Galactosamine (GalN) depletes UTP primarily in liver, resulting in decreased RNA synthesis in hepatocytes. When given together with a sublethal dose of lipopolysaccharide (LPS), GalN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. Melatonin is a cytokine modulator, antioxidant and anti-apoptotic agent. In the present study, we investigated the effect of melatonin on LPS-induced apoptotic liver damage in GalN-sensitized mice. Female CD-1 mice were intraperitoneally (i.p.) injected with melatonin (5.0mg/kg) 30min before GalN/LPS (700mg10μg/kg, i.p.), another two doses of melatonin (2.5mg/kg, i.p.) being administered 1 and 2h after GalN/LPS. Results showed that serum alanine aminotransferase (ALT) activities were markedly increased 8h after GalN/LPS treatment, massive hemorrhage being observed in histological sections of liver from GalN/LPS-treated mice. Melatonin significantly attenuated GalN/LPS-induced elevation of serum ALT. In parallel, melatonin distinctly improved GalN/LPS-induced congestion. Additional experiment showed that melatonin significantly attenuated GalN/LPS-induced hepatic apoptosis, measured by inhibition of caspase-3 activities and attenuation of DNA laddering. Furthermore, melatonin markedly increased hepatic Se-dependent glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) activities and attenuated hepatic glutathione (GSH) depletion in GalN/LPS-treated mice. Increases in serum tumor necrosis factor alpha (TNF-α), which were observed in GalN/LPS-treated mice, were significantly reduced by melatonin. However, melatonin had no effect on LPS-evoked nitric oxide production in GalN-sensitized mice. Taken together, these results indicate that melatonin protected against LPS-induced liver damage in GalN-sensitized mice through its strong ROS—scavenging, antiinflammatory and antiapoptotic effects.