Effects of dietary selenite,copper, and zinc on tissue trace mineral levels in chicks

Studies were conducted to determine whether nutritional selenium (Se) status affects the nutritional status of the chick with respect to other trace elements, particularly copper (Cu) and Zinc (Zn). Severe Se deficiency was produced in chicks by the use of diets that contained exceedingly low contents (less than 0.010 ppm) of Se, but contained adequate amounts of all other known essential nutrients. This diet was based upon corn and soybean meal produced in areas of China with endemic Se deficiency of geobotanical origin. A level of at least 0.10 ppm Se was found to be required to maintain normal Se status of chicks fed this diet, and Se deficiency resulted in decreased levels of Cu, Zn, and molybdenum in the pancreas (liver and plasma levels were not affected). High dietary supplementation of Zn nor Cu did not affect the short-term utilization of Se, as indicated by the 18-h responses of Se-dependent glutathione peroxidase in plasma and liver.     

Host selenium deficiency increases the severity of chronic inflammatory myopathy in Trypanosoma cruzi-inoculated mice

Weanling C3H/HeN mice were fed either a torula yeast-based diet deficient in selenium (Se) or the same diet supplemented with 0.2 ppm Se as sodium selenite. After 4 wk of feeding, the mice were inoculated intraperitoneally with the CA-I strain (clone K98) of Trypanosoma cruzi (TC). Before inoculation, mean serum Se levels were 430 versus 61 ng/ml in adequate and deficient mice, respectively. During the ascending phase of parasitemia, the Se-deficient mice exhibited significantly higher levels of parasites at 22-34 days postinfection (PI). However, no difference was found in the subsequent descending phase. As judged by visual examination at 2-mo-PI, some Se-deficient infected mice presented clinical signs of motor dysfunction. At 3-mo-PI, the end of the observation period, this chronic disease developed into a hind limb flaccid paralysis affecting 5 of 8 infected deficient mice. No signs of paralysis were seen in noninfected mice fed either diet or in infected mice fed the Se-adequate diet. At the histological level, both Se-adequate and Se-deficient infected mice showed mild myocarditis and moderate to severe myositis, with increasing intensity from 1- to 3-mo-PI in both groups. However, the severity of myositis was always more intense in the Se-deficient mice so that prominent areas of skeletal muscle replaced by fibrotic tissue were frequently observed. Thus, it can be concluded that Se deficiency in the murine host increases the severity of TC-induced myositis.     

Selenium and immune cell functions. II. Effect on lymphocyte-mediated cytotoxicity

Selenium (Se) is an essential nutritional factor with a chemopreventive potential. This study examined the ability of C57BL/6J mice, maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets, to generate cytotoxic lymphocytes (CTL) and to destroy tumor cells. CTL were generated in vivo by intraperitoneal immunization with P815 cells and in vitro by allogeneic stimulation of cells from animals maintained on a normal diet in media supplemented with 1 x 10(-9) to 1 x 10(-6) M Se (as selenite). Lymphocytes from animals maintained on the Se-supplemented diet had a greater ability to destroy tumor cells than lymphocytes from animals maintained on the normal diet, whereas Se deficiency reduced the cytotoxicity. The effects on cytotoxicity were accompanied by parallel changes in the levels of lymphotoxin produced. The greatest enhancement of tumor cytodestruction occurred with supplementation of 1 x 10(-7) M Se, whereas with 1 x 10(-6) M there was inhibition of the cytotoxic responses. The stimulatory effect of Se occurred during the phase of CTL generation rather than during the lytic phase of cytotoxicity. These results indicated that Se supplementation enhances CTL generation and the ability of a host to destroy malignant cells, whereas Se deficiency has the opposite effect.     

硒对大鼠心、肝、肌、胰、肺和肾脏细胞线粒体~(45)Ca摄取的影响

用低硒饲料和该饲料补硒分别喂大鼠,对比观察硒对动物心、肝,肌、胰、肺和肾脏线粗体~(45)Ca摄取及心肌线粒体呼吸的影响。结果表明硒非常显著地刺激此六脏器细胞线粒体钙摄取,其中,对心、肝、肌的刺激强大而稳定;对胰、肺,在温育过程中逐渐增强;对肾则稍差。硒还非常显著地刺激心肌线粒体呼吸功能。提示硒对维持整体线粒体钙运转及心肌线粒体呼吸功能具重要作用。     

Effect of selenium depletion and supplementation on the kinetics of type 1 5′-iodothyronine deiodinase and T3/T4 in rats

Presently, the effect of selenium (Se) deficiency and excess of Se (1 ppm) on the activity of selenoenzymes type 1 5′-iodothyronine deiodinase (5′-DI), glutathione peroxidase (GSH-Px), and level of thyroid hormones (T₃ and T₄) was studied in rats. Se levels in the serum and liver, T₃ and T₄ in the serum, GSH-Px levels in the liver, and 5′-DI activity in the liver/aorta/thyroid were estimated after 1, 2, and 3 mo of Se-deficient (0.02 ppm), Se-adequate (0.2 ppm), and Se-excess (1 ppm) diet feeding. All of these parameters decreased significantly in the Se-deficient group as compared to the adequate group. Within the deficient group, as the Se deficiency progressed, all of the parameters except 5′-DI decreased after 2 and 3 mo in comparison to 1-mo data. Thyroidal 5′-DI activity in Se deficiency showed the maximum increase. A significant increase was observed in all of the above parameters in the 1 ppm Se-supplemented diet group when compared with the adequate Se group; also, as the Se deposition increased within the Se-excess diet group, a significant increase was observed in all of the above parameters. However, as observed by others, the intake of excess of Se (i.e., 2 ppm in the diet) did not elevate the activities of selenoenzymes and thyroid hormones; rather, it had adverse effects. The present study concludes that Se supplementation at least up to 1 ppm enhances the selenoenzyme activities, and above this level, it may not be considered as an indicator of selenoenzyme activities.     

Morphofunctional analysis of zinc-accumulating capacity of digestive system organs]

The distribution of zinc and related changes have been studied in zinc--loaded chick pancreas, ileum and liver at the ultrastructural level by sulphide--silver method. White Leghorn chicks fed a high zinc diets (50, 500, 1000, 2000 and 4000 mgZn/kg diet) for 6 weeks, were killed at intervals; portions of their organs were fixed for light and electron microscopy; other samples were analyzed for zinc by AA spectrophotometry. A drastic increase of zinc level in chick pancreas fed 2000 mg Zn/kg diet (as ZnCl2) was associated with acinar cell degeneration. Apoptosis was the predominant form of acinar cell deletion. This study provides support for a previously proposed theory that cell injury stimulates passive zinc accumulation.     

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.     

Progressive defects observed in mouse sperm during the course of three generations of selenium deficiency

Three successive generations of mice were fed a Torula yeast based Se-deficient diet with or without 0.1 ppm Se in the drinking water. The Se-deficient mice, in the course of three generations, showed a decrease in body weight, testis weight, epididymal weight, and sperm production. The percentage of morphologically abnormal sperm increased in successive generations. The majority of sperm defects were found in the midpiece region of the tail. Many of these aberrant sperm were motile. A progressive decrease in fertility was noted during the first two generations of Se deficiency. This system confirms the essential role of Se in spermatogenesis and provides a model for the evaluation of the primary effect of Se deprivation on the structural development of sperm.     

Selenium and immune cell functions. I. Effect on lymphocyte proliferation and production of interleukin 1 and interleukin 2

The dietary intake of selenium (Se) has been shown to influence the development and expression of various biologic processes. This study examined the immunologic competence of lymphocytes from C57BL/6J mice maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se, as sodium selenite), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets. The ability of the cells to recognize alloantigens, to proliferate in response to stimuli, and to produce interleukin 2 (IL-2) was determined. Se deficiency significantly inhibited the ability of the lymphocytes to proliferate in response to allogeneic stimulation in the mixed lymphocyte reaction or to mitogen stimulation by phytohemagglutinin, whereas Se supplementation significantly enhanced both responses. In contrast, the amounts of IL-2 and interleukin 1 (IL-1) produced by lymphocytes and macrophages, respectively, removed from Se-deficient or Se-supplemented animals did not differ significantly from the amounts of IL-2 and IL-1 produced by cells removed from animals maintained on the control diet. These results suggest that the mechanism(s) responsible for the observed effects of Se on lymphocyte proliferation are independent of the levels of IL-2 or IL-1.     

Effects of dietary iron overload on glutathione peroxidase knockout mice

Excess iron (Fe) intake has been associated with an increased risk of cardiovascular disease in humans, presumably the result of increased oxidative stress. Previous work by us has shown that feeding a high-Fe diet to selenium (Se)-deficient weanling mice for 4 wk resulted in elevated plasma cholesterol and triglycerides and increased hepatic thiobarbituric acid reactive substances (TBARS). Here, we report the effect of Fe overload in mice lacking cellular glutathione peroxidase (GPX1 knockout [KO] mice), the selenoenzyme thought to account for much of the antioxidant action of Se. Four groups of 9–13 weanling wild-type (WT) or GPX1 KO mice were randomly assigned, then fed either an Fe-adequate (35 ppm Fe) or high-Fe (1100 ppm Fe) casein-based diet for 4 wk. Iron was added as ferric citrate. Both diets also contained 0.2 ppm Se added as sodium selenite. As expected, liver GPX1 activity was essentially absent in the KO mice. Another Se parameter measured (hepatic thioredoxin reductase activity) did not vary across groups. Although liver Fe was elevated in mice fed the high-Fe diet, liver TBARS was largely unaffected either by mouse genotype or diet fed. Moreover, plasma lipids were not elevated in the Fe-overloaded GPX1 KO mice. Thus, decreased GPX1 activity cannot account for the pro-oxidant hyperlipidemic effects observed earlier in mice fed the high-Fe Se-deficient diet. This suggests that impairment of Se functions other than GPX1 activity may be responsible for the elevated plasma lipids and hepatic TBARS seen in the Fe-overloaded Se-deficient mice.     

Influence of selenium deficiency on vital functions in rats

To clarify the relationship between selenium (Se) deficiency and functional disorders, the authors determined the Se concentration, anti-oxidant enzyme activity, and other parameters in rats fed a Se-deficient diet. Rats fed the Se-deficient diet showed a decrease in Se concentration and glutathione peroxidase (GSH-Px) activity in plasma, erythrocytes, heart, liver, and skeletal muscle from the first week after the initiation of the diet, an increase in heart lipid peroxide concentration from the second week, and an increase in liver glutathione S-transferase activity from the fourth week. From the twelfth week, a decrease in the growth rate in the rats fed the Se-deficient diet was observed. In spite of this growth impairment, no changes in electrocardiogram, muscle tone, degree of hemolysis, plasma biochemistry, or hematological values were detected. In summary, the authors found that a reduction of body Se is easily induced, but that the appearance of functional disorders following Se deficiency is difficult to detect in rats.     

Changes in blood chemistry, hematology, and histology caused by a selenium/vitamin E deficiency and recovery in chicks

Exudative diathesis, a condition caused by a selenium (Se)/vitamin E deficiency, was studied in chicks. Trios of chicks that showed clinical signs of exudative diathesis were matched for severity. One was injected subcutaneously with 0.5 mL distilled water, and the other two received 15 μg of Se in 0.5 mL distilled water. A chick fed a diet with supplemental Se also received 0.5 mL distilled water. Blood was collected from three chicks 2 d after injection, and from the other chick, 6 d after injection. After blood was collected, pectoral muscle and bone marrow were collected. Deficient chicks showed varying degrees of necrosis in pectoral muscle, whereas recovring chicks had extensive fibrosis in pectoral muscle. An analysis of blood showed differences in CO₂, glucose, Se, glutathione peroxidase, alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Heterophils and monocytes were increased in deficient chicks; lymphocytes, basophils, and hemoglobin decreased. After 6 d of recovery, all of the changes noted above were correcting toward normal. Eosinophils, in contrast, were unaffected by a deficiency, but increased in recovering chicks. It is hypothesized that cytokines associated with the inflammatory response accentuate the clinical signs of exudative diathesis.     

Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase

Protein-tyrosine phosphatase 1B (PTP1B) and T cell protein-tyrosine phosphatase (TCPTP) are closely related intracellular phosphatases implicated in the control of glucose homeostasis. PTP1B and TCPTP can function coordinately to regulate protein tyrosine kinase signaling, and PTP1B has been implicated previously in the regulation of endoplasmic reticulum (ER) stress. In this study, we assessed the roles of PTP1B and TCPTP in regulating ER stress in the endocrine pancreas. PTP1B and TCPTP expression was determined in pancreases from chow and high fat fed mice and the impact of PTP1B and TCPTP over- or underexpression on palmitate- or tunicamycin-induced ER stress signaling assessed in MIN6 insulinoma β cells. PTP1B expression was increased, and TCPTP expression decreased in pancreases of mice fed a high fat diet, as well as in MIN6 cells treated with palmitate. PTP1B overexpression or TCPTP knockdown in MIN6 cells mitigated palmitate- or tunicamycin-induced PERK/eIF2α ER stress signaling, whereas PTP1B deficiency enhanced ER stress. Moreover, PTP1B deficiency increased ER stress-induced cell death, whereas TCPTP deficiency protected MIN6 cells from ER stress-induced death. ER stress coincided with the inhibition of Src family kinases (SFKs), which was exacerbated by PTP1B overexpression and largely prevented by TCPTP knockdown. Pharmacological inhibition of SFKs ameliorated the protective effect of TCPTP deficiency on ER stress-induced cell death. These results demonstrate that PTP1B and TCPTP play nonredundant roles in modulating ER stress in pancreatic β cells and suggest that changes in PTP1B and TCPTP expression may serve as an adaptive response for the mitigation of chronic ER stress.     

The selenium intake of the female chicken influences the selenium status of her progeny

The primary purpose of this study is to determine the extent to which the effects of dietary supplementation of the female chicken with selenium (Se) continue into the next generation. An additional aim is to compare the relative effectiveness of pre-hatch (from the hen's diet) with that of post-hatch (from the progeny's diet) supplementation with Se on the Se status of the chick during the first 4 weeks of post-hatch life. Hens were maintained on control or Se-supplemented diets, respectively containing 0.027 and 0.419 μg Se/g of feed. The high-Se diet elevated the Se content of the hens' eggs by 7.1-fold. At hatch, the concentrations of Se in the liver, breast muscle and whole blood of the chicks originating from the high-Se parents were, respectively, 5.4-, 4.3- and 7.7-fold higher than the values in the chicks of the low-Se parents. When the offspring from the two parental groups were both maintained on the low-Se progeny diet, the tissue Se concentrations in chicks originating from the high-Se hens remained significantly higher for 3–4 weeks after hatching, compared with the values in chicks from the low-Se hens. Similarly, tissue glutathione peroxidase activity remained significantly higher in chicks from the high-Se hens for 2–4 weeks post-hatch. Thus, the effects of maternal Se supplementation persist in the progeny for several weeks after hatching. However, when chicks hatching from low-Se eggs were placed on a high Se diet, their tissue Se concentrations at 7 days of age were markedly higher than the values in chicks from high-Se eggs placed on the low-Se diet.     

克山病病区粮喂养大鼠红细胞膜脂流动性的变化

本文观察了低硒的克山病病区粮和克山病病区粮补硒后喂养大鼠对其红细胞膜脂流动性的影响。实验结果表明克山病病区粮喂养的大鼠红细胞膜脂流动性较正常对照降低,其原因可能与机体处于低硒状态下红细胞膜结合硒含量降低、红细胞膜胆固醇含量及脂质过氧化产物升高有关,克山病病区粮补硒后喂养大鼠,其红细胞膜脂流动性恢复至正常对照。     

Effects of aurothioglucose and dietary se on glutathione S-Transferase activities and glutathione concentrations in chick tissues

Experiments were conducted to determine whether the increased glutathione S-transferase (GSH-T) activity associated with selenium (Se) deficiency is necessarily related to losses in the activity of Se-dependent glutathione peroxidase (SeGSHpx) in chicks. Nutritional Se status was altered in two ways: by treatment with an antagonist of Se utilization, aurothioglucose (AuTG), and by feeding diets containing excess Se. Chicks given AuTG (10–30 mg AU/kg, sc) had growth rates and hepatic GSH concentrations that were comparable to those of saline-treated controls; however, their plasma GSH levels exceeded those of either Se-deficient (6-fold) or-adequate (3-fold) saline-treated chicks. Hepatic SeGSHpx activities of AuTG-treated chicks were hals those of controls under conditions of Se-adequacy; however, this effect was not detected when Se was deficient. Hepatic GSH-T_CDNB (assayed with 1-chloro-2,4-dinitrobenzene) activities of AuTG-treated chicks were significantly greater than those of controls when Se was deficient (i.e., when SeGSHpx activity was 12% of the Se-adequate level); however, deprivation of Se did not affect GSH-T_CDNB activity in the absence of AuTG. chicks fed excess Se (6–20 ppm as Na₂SeO₃) in diets containing either low (2 IU/kg) or adequate (100 IU/kg) VE, showed hepatic GSH-T_CDNB activities and GSH concentrations greater than those of Se-adequate (0.2 ppm Se) chicks by 100% and 40%, respectively. That increased hepatic GSH-T_CDNB activity can occur because of either AuTG or excess Se status under conditions wherein SeGSHpx activity is not affected indicates that the transferase response is not directly related to changes in the peroxidase.     

Hypercholesterolemia and tissue-specific differential mRNA expression of type-1 5'-iodothyronine deiodinase under different selenium status in rats

Type-1 5'-iodothyronine deiodinase (5'-DI) is responsible for conversion of T4 to T3. Selenium (Se) is an integral part of this enzyme. Keeping in view the strong association between atherosclerosis and hypothyroidism, the present study examined the behavior of 5'-DI in liver, aorta and thyroid during hypercholesterolemia following different Se status, i.e., Se deficiency (0.02 ppm), adequate (0.2 ppm) and excess dose (1 ppm) in SD male rats. Animals were fed a control or high-cholesterol diet (2%) for 1 and 2 months. 5'-DI activity and mRNA expression was measured by RIA and RT-PCR respectively. In liver and aorta, 5'-DI expression significantly decreased with the Se-deficient and the high-cholesterol diet. The trend was opposite in thyroid, i.e., mRNA expression increased significantly during selenium deficiency and with a high-cholesterol feeding. But with 1 ppm Se supplementation, the 5'-DI expression increased in all the three tissues. The present study indicates that hypercholesterolemia along with selenium deficiency is co-responsible for differential regulation of 5'-DI enzyme in thyroidal vs. extrathyroidal tissues. Distinct regulation of 5'-DI in the thyroid reflects the clinical importance of this selenoprotein during hypercholesterolemia as this enzyme is essential for T3 production, which further has a vital role in the maintenance of lipid metabolism.     

Effect of selenium and vitamin E dietary deficiencies on chick lymphoid organ development

Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (alpha-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.     

Minimum Selenium Requirements Increase When Repleting Second-Generation Selenium-Deficient Rats but Are Not Further Altered by Vitamin E Deficiency

Second-generation selenium-deficient weanling rats fed graded levels of dietary Se were used (a) to study the impact of initial Se deficiency on dietary Se requirements; (b) to determine if further decreases in selenoperoxidase expression, especially glutathione peroxidase 4 (Gpx4), affect growth or gross disease; and (c) to examine the impact of vitamin E deficiency on biochemical and molecular biomarkers of Se status. Rats were fed a vitamin E-deficient and Se-deficient crystalline amino acid diet (3 ng Se/g diet) or that diet supplemented with 100 μg/g all-rac-α-tocopheryl acetate and/or 0, 0.02, 0.05, 0.075, 0.1, or 0.2 μg Se/g diet as Na₂SeO₃ for 28 days. Se-supplemented rats grew 6.91 g/day as compared to 2.17 and 3.87 g/day for vitamin E-deficient/Se-deficient and vitamin E-supplemented/Se-deficient groups, respectively. In Se-deficient rats, liver Se, plasma Gpx3, red blood cell Gpx1, liver Gpx1 and Gpx4 activities, and liver Gpx1 mRNA levels decreased to <1, <1, 21, 1.6, 49, and 11 %, respectively, of levels in rats fed 0.2 μg Se/g diet. For all biomarkers, ANOVA indicated significant effects of dietary Se, but no significant effects of vitamin E or vitamin E × Se interaction, showing that vitamin E deficiency, even in severely Se-deficient rat pups, does not result in compensatory changes in these biochemical and molecular biomarkers of selenoprotein expression. Se requirements determined in this study, however, were >50 % higher than in previous studies that started with Se-adequate rats, demonstrating that dietary Se requirements determined using initially Se-deficient animals can result in overestimation of Se requirements.