Dietary selenium levels determine epidermal langerhans cell numbers in mice

Selenium (Se) is a dietary trace element that is essential for effective immunity and protection from oxidative damage induced by ultraviolet radiation (UVR). Langerhans cells (LC) represent the major antigen-presenting cells resident in the epidermis; a proportion migrate from the skin to the draining lymph nodes in response to UVR. Because it is known that Se deficiency impairs immune function, we determined what effect this has on LC numbers. CH3/HeN mice were weaned at 3 wk and placed on diets containing <0.005 ppm of Se (Se deficient) or 0.1 ppm of Se (Se adequate, control mice). After 5 wk on the diet, the epidermal LC numbers in the Se-adequate group were 966±51 cells/mm² and LC counts in the epidermis of the Se-deficient mice were 49% lower (p<0.05). Glutathione peroxidase-I (GPx) activity was measured in the epidermis, lymph nodes, and liver. In the epidermis, the activity of GPx in the Se-deficient mice was only 39% (p<0.01) of that seen in epidermis from Se-adequate mice (1.732 U/mg protein). The mice were then irradiated with one dose of 1440 J/m² of broadband UVB or mock irradiated. After 24 h, the decrease in LC number after UVB was greater in the Se-adequate mice, (40% decrease) compared to the Se-deficient group (10%). Thus, Se deficiency reduces epidermal LC numbers, an effect that might compromise cutaneous immunity.     

A Selenium-deficient Caco-2 Cell Model for Assessing Differential Incorporation of Chemical or Food Selenium into Glutathione Peroxidase

Assessing the ability of a selenium (Se) sample to induce cellular glutathione peroxidase (GPx) activity in Se-deficient animals is the most commonly used method to determine Se bioavailability. Our goal is to establish a Se-deficient cell culture model with differential incorporation of Se chemical forms into GPx, which may complement the in vivo studies. In the present study, we developed a Se-deficient Caco-2 cell model with a serum gradual reduction method. It is well recognized that selenomethionine (SeMet) is the major nutritional source of Se; therefore, SeMet, selenite, or methylselenocysteine (SeMSC) was added to cell culture media with different concentrations and treatment time points. We found that selenite and SeMSC induced GPx more rapidly than SeMet. However, SeMet was better retained as it is incorporated into proteins in place of methionine; compared with 8-, 24-, or 48-h treatment, 72-h Se treatment was a more sensitive time point to measure the potential of GPx induction in all tested concentrations. Based on induction of GPx activity, the cellular bioavailability of Se from an extract of selenobroccoli after a simulated gastrointestinal digestion was comparable with that of SeMSC and SeMet. These in vitro data are, for the first time, consistent with previous published data regarding selenite and SeMet bioavailability in animal models and Se chemical speciation studies with broccoli. Thus, Se-deficient Caco-2 cell model with differential incorporation of chemical or food forms of Se into GPx provides a new tool to study the cellular mechanisms of Se bioavailability.     

Effects of long-term selenium deficiency on glutathione peroxidase and thioredoxin reductase activities and expressions in rat aorta

The objective of this work was to determine whether long-term selenium (Se) deficiency might affect the antioxidant capacity of rat aorta, and the activities and expressions of glutathione peroxidase (GPx) and thioredoxin reductase (TR) in rat arterial walls. Weanling male Wister rats were fed Se-deficient or Se-adequate diets for 12 months. For the Se supplementation, sodium selenite was supplemented in drinking water (1 microg Se/ml) for 1 month. The aorta isolated from these groups were used to determine activities and mRNA levels. In comparison with the control, the activity and expression of GPx, superoxide dismutase activity and the total antioxidant capacity were significantly decreased in Se-deficient rats arterial walls. Following Se supplementation, they were restored to different extents. The content of malondialdehyde was increased markedly in Se-deficient rats. There seems an inverse relationship between the dietary Se and the activity and expression of TR. A positive relationship exists between dietary Se and the antioxidant capacity of rat arterial walls. The activities and expressions of GPx and TR in arterial walls were regulated by selenium by different mechanisms. Regulation of the expression of TR was mediated by reactive oxygen species, but of GPx by selenium status. The thioredoxin system may be the major cellular redox signaling system in rat arteries, rather than the glutathione system.     

Effect of long-term Se deficiency on the antioxidant capacities of rat vascular tissue

Selenium (Se) is an essential micronutrient in human health and Se deficiency has been incriminated in the etiology of cardiovascular diseases. However, the effect of long-term Se deficiency on the antioxidant capacities of vascular tissue has not been elucidated. This study was to determine whether long-term Se deficiency might affect the antioxidant capacity of rat vascular tissue and whether the diet Se might affect the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR) in rat vascular tissue. Weanling male Wister rats were fed Se-deficient and Se-adequate diets for 12 mo. Se was supplemented in drinking water (1 μg Se/mL) for 1 mo. The arterial walls isolated from various groups were used in the assay. In comparison with the control, Se-deficient rats exhibited significant decreases of GPx activity and total antioxidant capacity in the arterial wall. Similar decreases appeared in the heart, liver, and kidney. The superoxide dismutase activity was also decreased in the Se-deficient rat’s arterial wall. Followed by Se supplementation, they were restored to different extent. TR activity was decreased in the heart, liver, and kidney, but increased in the arterial wall. The content of malondialdehyde was increased markedly in Se-deficient rats. In conclusion, a positive correlation exists between dietary Se and antioxidant capacity of rat vascular tissue except TR. It seems that the activities of GPx and TR in the rat arterial wall were mediated in different pathways by the Se status.     

Regulation of the insulin antagonistic protein tyrosine phosphatase 1B by dietary Se studied in growing rats

Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counterregulation of insulin signaling, and its physiological modulation depends on H2O2 and glutathione (GSH). Se via GSH peroxidases (GPxs) and its specific metabolism is involved in the removal of H2O2 and in the regulation of GSH metabolism. Recent results from animal trials and epidemiological studies with humans have shown that a high GPx1 activity or a permanent surplus of Se may promote the development of obesity and diabetes. Our nutrition physiological study with 7 x 7 growing rats was carried out to examine if PTP1B is modulated by Se supplements and, thus, may represent one trigger mediating these undesirable metabolic effects of Se. One group of rats was fed an Se-deficient diet for 8 weeks. The diets of the other six groups contained Se as selenite or selenate according to the recommendations (0.20 mg/kg diet) and at two supranutritional levels (1.00 and 2.00 mg/kg diet). All Se-supplemented animals featured a significantly higher body weight (6-14%) compared to their Se-deficient companions. Expression and activity of GPx1 in the liver of Se supplemented animals was 10- and 70-fold higher compared to Se deficiency. The detailed study of PTP1B regulation using an enzymatic assay and Western Blot analysis with an antibody against protein glutathionylation revealed that PTP1B was significantly up-regulated by both a maximization of GPx1 activity and by increasing dietary Se supply, reducing its inhibition via glutathionylation. Selenate effected a stronger PTP activation compared to selenite. In conclusion, our results suggest that the modulation of PTP1B activity may represent one plausible mechanism by which a long-term intake of Se supplements exceeding the requirements can promote the development of obesity and diabetes and needs further intensive investigation.     

Selenium Deficiency Is Associated with Endoplasmic Reticulum Stress in a Rat Model of Cardiac Malfunction

The relationship between selenium (Se) deficiency-induced cardiac malfunction and endoplasmic reticulum (ER) stress is poorly understood. In the present study, 18 weaning Sprague Dawley rats were randomly fed with three different Se diets, and myocardial glutathione peroxidase (GPx) activity was measured by an enzyme activity assay. Cardiac function was evaluated by hemodynamic parameters. ER stress markers immunoglobulin-binding protein (BiP)/glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were detected by western blotting. Our data showed that myocardial GPx activity and cardiac function were conspicuously impaired in Se-deficient rats. Expression of GRP78 and CHOP was significantly upregulated by treatment of Se deficiency. Improvements in myocardial GPx activity and cardiac function, as well as decreases in expression of GRP78 and CHOP, were observed after Se supplementation. Consequently, our data show that ER stress was involved in Se deficiency-induced cardiac dysfunction.     

Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium

Cadmium (Cd) is an ubiquitous environmental pollutant that has been associated with male reproductive toxicity in animal models. However, little is known about the reproductive toxicity of Cd in birds. To investigate the toxicity of Cd on male reproduction in birds and the protective effects of selenium (Se) against subchronic exposure to dietary Cd, 100-day-old cocks received either Se (as 10 mg Na₂SeO₃ per kg of diet), Cd (as 150 mg CdCl₂ per kg of diet) or Cd + Se in their diets for 60 days. Histological and ultrastructural changes in the testis, the concentrations of Cd and Se, amount of lipid peroxidation (LPO), the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx), and apoptosis and serum testosterone levels were determined. Exposure to Cd significantly lowered SOD and GPx activity, Se content in the testicular tissue, and serum testosterone levels. It increased the amount of LPO, the numbers of apoptotic cells and Cd concentration and caused obvious histopathological changes in the testes. Concurrent treatment with Se reduced the Cd-induced histopathological changes in the testis, oxidative stress, endocrine disorder and apoptosis, suggesting that the toxic effects of cadmium on the testes is ameliorated by Se. Se supplementation also modified the distribution of Cd in the testis.     

Effect of Different Selemethionine Forms and Levels on Performance of Breeder Hens and Se Distribution of Tissue and Egg Inclusion

A 2 × 2 factorial arrangement of treatments in randomized design was conducted to investigate the effect of different selenomethionine (SM) sources and levels on the productive performance of breeder hens and the Se distribution in the inclusion of eggs and serum and tissues of breeder hens and its offspring. A total of 480 Ling-Nan-Huang breeder hens, 48 weeks of age, were allocated to four treatments, each of which included three replicates of 40 hens. Pretreatment period was 2 weeks, and the experiment lasted 8 weeks. Two SM forms of dl-SM and l-SM were supplemented at 0.15 or 0.30 mg Se/kg into the basal diet. Results showed that the Se level of 0.15 mg/kg supplemented in the diet, compared to 0.30 mg/kg, significantly elevated the percentage of egg production (p < 0.05), hatchability (p < 0.01), and birthrate (p < 0.01), whereas the Se level of 0.30 mg/kg led to a higher Se content in egg contents, serum, and all tissues (p < 0.01). In addition, the form of dl-SM showed a significant increase in Se content of egg inclusion (p < 0.01), serum (p < 0.01), and all tissues (p < 0.01, except breeder hens’ pancreas and its offspring’s liver and breast muscle). The birthrate and yolk Se content were markedly influenced by the interaction between Se source and Se level (p < 0.01). The above results suggested that dl-SM, compared to l-SM, had a similar equal effect on the performance of breeder hens, but dl-SM was superior to l-SM with respect to selenium distribution in egg inclusion, serum, and tissues.     

Maternal selenium deficiency increases hydrogen peroxide and total lipid peroxides in porcine fetal liver

To investigate the role of selenium (Se) in the developing porcine fetus, prepubertal gilts (n=42) were randomly assigned to either Se-adequate (0.39 ppm Se) or Se-deficient (0.05 ppm Se) gestation diets 6 wk prior to breeding. Maternal and fetal liver was collected at d 30, 45, 70, 90, and 114 of pregnancy. Concentrations of Se in maternal liver decreased during gestation in gilts fed the low-Se diet. The activity of cellular glutathione peroxidase (GPx) was decreased at d 30 and 45 of gestation in liver of gilts fed the low-Se diet. Concentrations of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were greater in liver homogenates from gilts fed the low-Se diet. Within the fetuses, liver Se decreased in those fetuses of gilts fed the low-Se diet. Although the activity of GPx in fetal liver was not affected by the maternal diet, concentrations of H₂O₂ and MDA in fetal liver were greater in fetuses from gilts fed the low-Se diet. Maternal liver GPx activity was approx 12-fold greater than fetal liver GPx activity regardless of dietary treatment. These results indicate that maternal dietary Se intake affects fetal liver Se concentration and feeding a low-Se diet during gestation increases oxidative stress to the fetus, as measured by fetal liver H₂O₂ and MDA.     

High-selenium lentil diet protects against arsenic-induced atherosclerosis in a mouse model

Background: Cardiovascular disease (CVD) is a major cause of death worldwide, and arsenic (As) intake, mainly through drinking water, is a well-known risk factor for CVD as well as other health problems. Selenium (Se) is a known antagonist to As toxicity. Objective: We tested the potential of high-Se lentils from the Canadian prairies as a therapeutic food to alter the outcome of As-enhanced atherosclerosis. Materials and Methods: Male ApoE^−/− mice exposed to a moderate level of As (200 ppb) in their drinking water, and control mice on tap water received one of three lentil diets: Se-deficient (0.009 mg/kg), Se-adequate (0.16 mg/kg) or Se-high (0.3 mg/kg). After 13 weeks, lesion formation in the aortic arch and sinus were assessed. Intralesional cellular composition, serum lipid levels and hepatic oxidative stress were assessed as well. Results: Arsenic-exacerbated plaque formation was reduced in the sinus and completely abolished in the aortic arch of mice on the Se-fortified lentil diet, whereas lesions were increased in As-exposed mice on both the Se-deficient and Se-adequate diets. Notably, Se deficiency contributed to proatherogenic composition of serum lipids in As-exposed mice as indicated by high-density lipoprotein:low-density lipoprotein. At least adequate Se status was crucial for counteracting As-induced oxidative stress. Conclusion: This study is the first to show the potential of high-Se lentils to protect against As-triggered atherosclerosis, and this invites further investigations in human populations at risk from As contamination of their drinking water.     

Activation of superoxide dismutase in selenium-deficient mice infected with influenza virus.

Selenium (Se) deficiency is associated with decreased activities of Se-dependent antioxidant enzymes, glutathione peroxidase (GPx) and thioredoxin reductase (TR), and with changes in the cellular redox status. We have previously shown that host Se deficiency is responsible for increased virulence of influenza virus in mice due to changes in the viral genome. The present study examines the antioxidant defense systems in the lung and liver of Se-deficient and Se-adequate mice infected with influenza A/Bangkok/1/79. Results show that neither Se status nor infection changed glutathione (GSH) concentration in the lung. Hepatic GSH concentration was lower in Se-deficient mice, but increased significantly day 5 post infection. No significant differences due to Se status or influenza infection were found in catalase activities. As expected, Se deficiency was associated with significant decreases in GPx and TR activities in both lung and liver. GPx activity increased in the lungs and decreased in the liver of Se-adequate mice in response to infection. Both Se deficiency and influenza infection had profound effects on the activity of superoxide dismutase (SOD). The hepatic SOD activity was higher in Se-deficient than Se-adequate mice before infection. However, following influenza infection, hepatic SOD activity in Se-adequate mice gradually increased. Influenza infection was associated with a significant increase of SOD activity in the lungs of Se-deficient, but not Se-adequate mice. The maximum of SOD activity coincided with the peak of pathogenesis in infected lungs. These data suggest that SOD activation in the lung and liver may be a part of a compensatory response to Se deficiency and/or influenza infection. However, SOD activation that leads to increased production of H(2)O(2) may also contribute to pathogenesis and to influenza virus mutation in lungs of Se-deficient mice.     

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

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

Trace Elements Status in Selenium-Deficient Rats—Interaction with Cadmium

Although the metabolic and toxicological interactions between essential element selenium (Se) and toxic element cadmium (Cd) have been reported for a long time, the experimental studies explored mostly acute, high-dose interactions. Limited data are available regarding the effects of Se-deficiency on toxicokinetics of cadmium, as well as on the levels of key trace elements—copper, zinc, and iron. In the present study, male and female Wistar weanling rats (n = 40/41) were fed either Se-deficient or Se-adequate diet (<0.06 or 0.14 mg Se per kilogram diet, respectively) for 12 weeks, and from week 9 were drinking water containing 0 or 50 mg Cd/l as cadmium chloride. At the end of the 12-week period, trace element concentrations were estimated by AAS. Selenium-deficient rats of both genders showed significantly lower accumulation of cadmium in the liver, compared to Se-adequate rats. Zinc and iron hepatic levels were not affected by Se-deficiency. However, a significant elevation of copper was found in the liver of Se-deficient rats of both genders. Cadmium supplementation increased zinc and decreased iron hepatic level, regardless of Se status and decreased copper concentration in Se-adequate rats. Se-deficiency was also found to influence the effectiveness of cadmium mobilization in male rats.     

Influence of high inorganic selenium and manganese diets for fattening pigs on oxidative stability and pork quality parameters

Data are scarce regarding combined high Se and Mn supplementation in livestock diets, however, as Se and Mn are functionally related as cofactors of glutathione peroxidase (GPx) and Mn-superoxide dismutase (SOD), respectively, beneficial synergistic effects on oxidative stability of tissues may result. This experiment evaluated the effect of an oversupply of Se and Mn within European legal limits compared with recommendations on performance, oxidative stability of the organism and meat quality in a randomised complete block design. A total of 60 crossbred gilts were fed maize–barley–soya bean meal diets formulated in a 2×2 factorial approach with inorganic Se (0.2 v. 0.5 mg/kg Se dry matter (DM)) or inorganic Mn (20 v. 150 mg/kg Mn DM) from 31 to 116 kg BW. Se supplementation reduced feed intake, whereas high Mn diets impaired average daily gain (P<0.05). Qualitative carcass characteristics were impaired by Se and Mn predominantly in the semimembranosus muscle. Activity of GPx in liver was increased by high Se diets (P<0.05). Mn supplementation increased catalase (CAT) activity in liver, GPx in plasma and total antioxidative capacity (TAC) in muscle, whereas it decreased CAT activity in plasma (P<0.05). Cu/Zn-SOD in muscle showed higher activity in high-Se-low-Mn diets but lower activity when both high Se and Mn were combined (Se×Mn P<0.05). Mn supplementation increased Mn concentration in longissimus thoracis et lumborum, but simultaneously reduced Se concentration (P<0.05). Upon retail display, Mn increased lipid oxidation more pronouncedly (higher thiobarbituric acid reactive substances; P<0.05) than Se (P<0.10). Despite some positive effects (Mn increased TAC, Se increased GPx, Se and Mn increased tenderness), no synergistic effects of high Se and Mn diets or an overall beneficial impact on meat quality, especially during storage, could be observed. Including the negative effects on performance, feeding Se and Mn up to the maximum legal level cannot be recommended.     

Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats

Twenty-four weanling male Wistar rats were divided into four groups fed diets containing adequate or deficient levels of selenium (0.5 ppm [+ Se] or <0.02 ppm [−Se] and protein (15% [+Pro] or 5% [−Pro]), but adequate levels of all other nutrients for 4 wk to determine the effects of Se deficiency and protein deficiency on tissue Se and glutathione peroxidase (GSHPx) activity in rats. Plasma, heart, liver, and kidney Se and GSHPx were significantly lower in Se-deficient groups in relation to Se-sufficient groups. In Se-deficient groups, Se and GSHPx were significantly higher in −Se−Pro rats in heart, liver, and kidney. Data analysis showed that there were significant interaction effects between dietary Se and protein on Se and GSHPx of rats. It is assumed that under the condition of Se deficiency. a low level of protein may decrease Se and GSHPx utilization, increase GSHPx synthesis, and result in Se redistribution. This could account for high levels of Se and GSHPx in the −Se−Pro rats compared to −Se+Pro rats.     

Effects of selenium supplementation on selenium status of farmed fallow deer in outdoor pens

The study investigated the effects of selenium (Se) supplementation on Se status in farmed fallow deer. Fallow deer were housed on grass pasture and adapted to consume ∼200 g of pelleted grain daily. Animals were divided into two groups. One group received pelleted grain enriched with sodium selenate for 12 weeks (Se+ group, N = 10). Se intake for the first 7 weeks was 0.18 mg/kg dry matter (DM) and 0.32 mg/kg DM for the subsequent 5 weeks. The control group was fed pelleted grain without extra Se (Se− group, N = 9, 0.06-0.08 mg/kg DM). Blood samples were collected at the beginning and the end of the experiment. After the animals were slaughtered, tissue samples were collected for analysis of Se concentrations and Se-dependent glutathione peroxidase 1 (GPx1) activity. In addition, Se-independent α-glutathione-S-transferase (α-GST) activity was analyzed in liver tissue. Se supplementation significantly increased Se levels in plasma and in tissues as follows: liver > spleen > skeletal muscle > myocardium > kidney. Se supplementation also significantly increased GPx1 activity in tissues in the following order: liver > skeletal muscle > spleen = myocardium > kidneys. However, hepatic α-GST activity did not differ between Se+ and Se− groups. As expected, Se supplementation increased blood and tissue Se concentrations and GPx1 activity, which suggests a better antioxidant status. However, the activity of α-GST, an important Se-independent antioxidant enzyme, was not altered, presumably because GPx provided an adequate antioxidant capacity even though Se intake was low.     

Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise eliminate them. Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation. Humans, like mouse strains, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total dermal area (expressed as mast cells per square millimeter). This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations. We hypothesize that mast cells function in humans, as in mouse strains, by initiating immunosuppression following UV irradiation and, thereby, allowing a permissive environment for the development of BCC. Thus, a high dermal mast cell prevalence as demonstrable in buttock skin is a significant predisposing factor for development of BCC in humans.     

Asperyellone pretreatment protects HaCaT cells from UVB irradiation induced oxidative damages: Assessment under in vitro and in vivo conditions and at molecular level

The present study explores the UVB protective role of Asperyellone (AY), a secondary metabolite of Aspergillus niger strain AN01. The in vitro UVB protective efficacy of AY was studied using the Human Epidermal keratinocytes cells (HaCaT) cell line. The results suggest the appreciable scavenging of UVB-induced reactive oxygen species in the AY-pretreated cells compared with UVB control. Experimental results on the antioxidant enzymes (Catalase, SOD, LPO, and GPx) profile, histochemical, and molecular analyses support the UVB protective effect of AY in HaCaT cells. Further, the in vivo UVB protective efficacy of AY was studied using animal models and compared with that of commercially available UVB protective agents. Physical, biochemical, and molecular analyses of skin samples emphasized the UVB protective role of AY. Thus, the important beneficial effects of AY have been explored in the present study.     

Selenium regulation of thioredoxin reductase activity and mRNA levels in rat liver

Mammalian thioredoxin reductase (TRR; NADPH₂:oxidized thioredoxin oxidoreductase, E.C. 1.6.4.5) is a new member of the family of selenocysteine-containing proteins. TRR activity in Se-deficient rat liver is reported to decrease to 4.5 to 15% of the activity in Se-adequate rat liver, similar to the fall in Se-dependent glutathione peroxidase-1 activity. Both glutathione peroxidase-1 enzyme activity and mRNA levels decrease dramatically in Se deficiency, whereas glutathione peroxidase-4 activity only decreases to 40% of Se-adequate levels and mRNA level is little affected by Se deficiency. The purpose of these experiments is to study the effect of Se status on TRR mRNA levels and enzyme activity in our well-characterized rat model, and to compare this regulation directly to the regulation of other Se-dependent proteins in male weanling rats fed Se-deficient diets or supplemented with dietary Se for 28 days. In two experiments, TRR activity in Se-deficient liver decreased to 15% of Se-adequate activity as compared to 2% and 40% of Se-adequate levels for GPX1 and GPX4, respectively. Using ribonuclease protection analysis, we found that TRR mRNA levels in Se-deficient rat liver decreased to 70% of Se-adequate levels. This decrease in TRR mRNA was similar to the GPX4 mRNA decrease in Se-deficient liver in these experiments, whereas GPX1 mRNA levels decreased to 23% of Se-adequate levels. This study clearly shows that TRR represents a third pattern of Se regulation with dramatic down-regulation of enzyme activity in Se deficiency but with only a modest decrease in mRNA level. The conservation of TRR mRNA in Se deficiency suggests that this is a valued enzyme; the loss of TRR activity in Se deficiency may be the cause of some signs of Se deficiency.