Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression,evoking oxidative stress,and activating inflammation and apoptosis

Background:The immune system is one aspect of health that is affected by dietary selenium(Se)levels and selenoprotein expression.Spleen is an important immune organ of the body,which is directly involved in cellular immunity.However,there are limited reports on Se levels and spleen health.Therefore,this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis.Methods:Twenty-four pure line castrated male Yorkshire pigs(45 days old,12.50±1.32 kg,12 full-sibling pairs)were divided into two equal groups and fed Se-deficient diet(0.007 mg Se/kg)or Se-adequate diet(0.3 mg Se/kg)for 16 weeks.At the end of the trial,blood and spleen were collected to assay for erythroid parameters,the osmotic fragility of erythrocytes,the spleen index,histology,terminal deoxynucleotidyl transferase nick-end labeling(TUNEL)staining,Se concentrations,the selenogenome,redox status,and signaling related inflammation and apoptosis.Results:Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes(P<0.05).The spleen index did not change,but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased,the red pulp increased,and splenocyte apoptosis occurred in the Se deficient group.Se deficiency decreased the Se concentration and selenoprotein expression in the spleen(P<0.05),blocked the glutathione and thioredoxin antioxidant systems,and led to redox imbalance.Se deficiency activated the NF-κB and HIF-1αtranscription factors,thus increasing pro-inflammatory cytokines(IL-1β,IL-6,IL-8,IL-17,and TNF-α),decreasing anti-inflammatory cytokines(IL-10,IL-13,and TGF-β)and increasing expression of the downstream genes COX-2 and iNOS(P<0.05),which in turn induced inflammation.In addition,Se-deficiency induced apoptosis through the mitochondrial pathway,upregulated apoptotic genes(Caspase3,Caspase8,and Bak),and downregulated antiapoptotic genes(Bcl-2)(P<0.05)at the mRNA level,thus verifying the results of TUNEL staining.Conclusions:These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins,oxidative stress,inflammation and apoptosis.

Further Investigation on the Role of Selenium Deficiency in the Aetiology and Pathogenesis of Keshan Disease

Selenium supplements were not able to restore the ultrastructural changes in the myocardiurn of latent Keshan disease patients taken by using cardiac catheter endomyocardial biopsy. Observations on the changes of seleniurn status and the incidence of Keshan disease showed that new latent and naturally-occurring chronic cases were found in the endemic area even after selenium levels had been elevated in the residents to the levels typical in the non-endemic area. These results indicate that although selenium deficiency might be a primary pathogenetic geogen in the occurrence of Keshan disease, it is rather a conditional predisposing factor than a specific or initiative aetiologic factor for the occurrence of Keshan disease. Selenium supplmentation could apparently alleviate the higher platelet responsiveness of residents in the endemic area, which might contribute to eliminating the basis for the occurrence of the multifocal perivascular necroses in myocardium of acute and subacute Keshan disease

Selenium and Iodine Deficiencies and Selenoprotein Function

This paper reviews some recent findings on the interactions between selenium deficiency and iodine deficency. Both micronutrients can control the levels of selenoprotein mRNAs, particularly in the thyroid and brain. When selenium and iodine supplies are limiting the compensatory mechanisms work to minimise adverse effects on thyroid hormone metabolsm and thus neurological developtnent. The mechanisms for regulation of selenoproteins in selenium and iodine deficiency are however very tissue-specific. For example, unlike the brain and thyroid,brown adipose tissue is unable to retain selenoproteins in selenium and iodine deficiency and is therefore at greater risk from injurious effects of the deficiencies.

Biochemical and Morphological Changes in the Lenses of Selenium and/or Vitamin E Deficient Rats

The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R),superoalde dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groupe, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SoD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioaldative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract

Studies on the Free Radicals and Thyroid Hormone Metabolism in Cattle with Iodine and Selenium Deficicncy

In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.

Preparation of Organic Selenocystine Using Locally Isolated Bread Yeast

In contrast to the toxic inorganic forms of selenium to life at very low concentrations, the organic-selenium compounds are of considerable interest and several of them play essential roles in cell biochemistry and nutritional science. Se-yeast （Selenium-enriched yeast） is a common form of selenium used to supplement dietary intake of this important trace mineral. In the present study, we tried to prepare an organic selenocystine using locally isolated bread yeast （Saccharomyces cerevisiae）. A novel locally prepared date extract media enriched by addition of 0.2% KH2PO4 （potassium phosphate）, 0.6% ammonium sulfate was adopted as alternative culture media. Differences concentrations of selenium salt （30, 60, 120 and 240 lag/mL） were added to the yeast culture media. While the best concentration of selenium added was 30Bg/mL, it achieved optimal conditions for the growth of yeast and the production of red yeast growth identical to the standard. The products （organic selenocystine） were analyzed by HPLC （High Performance Liquid Chromatography） and AAS （Atomic Absorption Spectrophotometer） comparing with authentic standard obtained from Sigma. Results confirmed the formation of similar selenocystine products.