|
|
Selenium deficiency increases the pathology of an influenza virus infection
"The data presented here demonstrate that a dietary deficiency of the nutritionally essential trace element Se increases the lung pathology caused by the influenza virus in mice. Under our conditions, mice fed a diet adequate in Se develop only a relatively mild inflammatory response when infected with influenza A/Bangkok/1/79. However, the inflammation is much more severe in Se-deprived mice. The increased severity of the inflammation is reflected in the increased number of inflammatory cells obtained by BAL as well as the higher pathology score."
|
Selenium
Nutritional, Toxicologic, and Clinical Aspects
"No completely satisfactory treatment of selenium toxicity
is available.13 The treatment of selenium poisoning suggested
in most references has been inadequate or even misleading."
"The toxicity of selenium can be altered by interactions
with other substances, including sulfate, methionine, cysteine,
various heavy metals, arsenic, and vitamins C and E.9
The function of selenium is intimately related to vitamin E
in normal metabolism. It has the capacity to detoxify heavy
metals by mutual interaction, but interaction between selenium
and other metabolites can either reduce or potentiate
selenium toxicity. Selenium can act as an antagonist
against various toxic metals, such as arsenic, cadmium,
copper, lead, mercury, silver, and zinc."
"Diets containing 4 to 5 ppm per day have been shown to inhibit
the growth of animals, and lower levels can be toxic if the
diet is deficient in vitamin E. Similarly, caries formation
may be increased if lower levels of selenium are consumed
during the development of teeth."
An incident occurred in 1983-1984 in the United States
during which 13 persons suffered toxic effects from ingesting
dietary supplement tablets containing high levels of
selenium as the result of a manufacturing error.'2"3 In
March 1984, selenium tablets distributed to 39 outlets in 15
states were recalled when an analysis of one lot revealed a
selenium content of 27.3 mg per tablet (182 times higher
than labeled). Subsequent analyses of tablets from all four
implicated distribution lots showed that each tablet contained
at least 25 mg of sodium selenite and 4 to 5 mg total
of elemental or organic selenium.
Illustrative of the toxicity of these supplements was the
case of a 57-year-old woman who had consumed 77 of the
90 tablets from a bottle when she learned of the recall and
consulted her physician. Her tablets were later found to
contain 31 mg of total selenium per tablet. The woman
noticed pronounced hair loss about 11 days after starting
the selenium supplement in late December 1983. This progressed
to almost total alopecia over a two-month period.
Later, horizontal white streaking on one fingernail, along
with tenderness and swelling of the fingertip and a purulent
periungual discharge, was noted. These changes subsequently
progressed to involve all fingernails. The fingernail
from the originally affected finger was eventually lost. She
also had periodic episodes of nausea and vomiting, a sourmilk
breath odor, and progressive fatigue. Her alopecia was
initially attributed to emotional stress consequent to the
death of her husband a year earlier. She was treated with
oral erythromycin for paronychia after consulting a dermatologist
in January 1984. In March 1984, her serum selenium
concentration was 528 ng per ml-two to four times
the normal level for the US population. Her estimated cumulative
dose was 2,387 mg of selenium. This woman was
also taking other vitamin supplements, and selenium toxicity
was thought to probably have been minimized by the
simultaneous ingestion of large doses of vitamin C. Other
persons who had consumed the mislabeled superpotent selenium
pills had similar symptoms with varying degrees of
severity.
Illustrative of the chronic toxic effects resulting from
occupational selenium exposure is the case of a man with a
50-year history of working in selenium refining who died of
a myocardial infarction and who at autopsy had red hair
and fingernails and numerous noncaseating granulomas in
the lungs."8 High selenium levels were found in the lungs,
peribronchial lymph nodes, hair, and nails. The selenium
level in the kidney was higher than that in the liver. In fact,
there was no accumulation of selenium in the liver, as might
be expected from findings in animal models. In humans the
target organ of chronic selenosis appears to be the lung,
which manifests acute "rose cold" or, as in this patient, a
long-term granulomatous hypersensitivity. In contrast, the
liver appears to be the target organ of chronic selenosis in
test animals.
|
Selenium Supplementation in Patients with Autoimmune Thyroiditis Decreases Thyroid Peroxidase Antibodies Concentrations
Roland Gärtner, Barbara C. H. Gasnier, Johannes W. Dietrich, Bjarne Krebs, and Matthias W. A. Angstwurm
The Journal of Clinical Endocrinology & Metabolism 2002 87:4, 1687-1691
In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 ± 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml.
Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by χ2 test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T4, and free T3 levels were unchanged in both groups.
We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.
DOI: http://dx.doi.org/10.1210/jcem.87.4.8421
Received: August 02, 2001
Accepted: January 14, 2002
Published Online: July 02, 2013
|
The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma
Roland Gärtner*, Werner Albrich and Matthias W. A. Angstwurm
Article first published online: 16 DEC 2008
DOI: 10.1002/biof.5520140125
The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including seps
|
Selenium and selenoproteins in health and disease.
"The beneficial role of the trace element selenium (Se) in human health has been known for several decades and is attributed both to low-molecular-weight Se compounds and to its presence within 25 selenoproteins in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins involves decoding of the UGA codon. This process requires multiple features, such as the Sec-insertion sequence (SECIS) element and protein factors, including a specific elongation factor EFSec and the SECIS-binding protein 2, SBP2. Although many selenoproteins remain functionally uncharacterized, some of their known functions include redox regulation of intracellular signaling, redox homeostasis, and thyroid hormone metabolism. Pathologically, reduced expression of selenoproteins has been directly linked with the congenital muscle disease referred to as selenoprotein N (SEPN)-related myopathy and with thyroid-hormone metabolism defects (deficiency of deiodinases due to genetic defects in SBP2). From a broader, less well defined aspect, selenium compounds and selenoproteins have been linked to prevention of some forms of cancer, Alzheimer's disease, cardiovascular disease, and life span. This forum summarizes recent advances in our understanding of important roles of selenium, selenoproteins, and factors involved in selenoprotein synthesis in health and disease and discusses potential targets for therapy."
|
Effect of Dietary Selenium on the Primary and Secondary Immune Response in Calves Challenged with Infectious Bovine Rhinotracheitis Virus
These results indicate that selenium deficiency may depress the immune response of calves challenged with a foreign pathogen.
|
Why Nature Chose Selenium
"The first recognized role of selenium in biology was as a toxin.
The investigation into the cause of “alkali disease” and “blind
staggers,” diseases of livestock in the American West and Plains
States by Kurt Franke and others, showed that these diseases
were forms of selenosis due to the ingestion of high doses of
selenium found in cereal crops, animal forage, and selenium
accumulator plants such as Astragalus (known commonly as
“locoweed”) grown in soils with high selenium content.21−24 It
is remarkable that Franke at a very early date was able to show
that the toxic form of selenium in locally grown grains was in
the protein fraction of sulfuric acid hydrosylates. His experiments
showed that selenium was “adsorbed on the protein
molecule.”
25 He was able to conclude that “There is evidence
that most of the selenium is in a compound very similar to
cystine.”
26 Franke’s prescience that selenium would replace the
sulfur atom of an amino acid is little recognized26 and predates
the discovery of the “21st” amino acid,27,28 selenocysteine, by
Thressa Stadtman29 by 40 years! It should be noted that, while
blind staggers is often attributed to selenosis, it may in fact be
caused by sulfate-related polioencephalomalacia due to
contamination of water sources by sodium sulfate and
magnesium sulfate."
" Second, it is
extremely costly in terms of the cellular energy currency, ATP,
to insert selenocysteine into a protein. It costs ∼25 mol of ATP
to insert 1 mol of cysteine into a protein.174 Given the multiple
accessory proteins required to insert selenocysteine into a
protein, the biosynthetic costs of a selenoprotein must be
considerably more than that of a cysteine-containing protein. A
third consideration for biology is the geological distribution of
selenium in the Earth’s crust, as sulfur is much more abundant
relative to selenium. This ratio is estimated to be as low as
6000:1175 and as high as 55 500:1.176 In addition, selenium is
not distributed evenly over the Earth’s crust.177 For example,
there are both seleniferous and selenium deficient areas of
China and the American west. Selenium deficient soils are
especially consequential in China, New Zealand, and Finland.83
This means that animal life on land does not have equal access
to this essential nutrient.
Considering the three factors mentioned above, it is natural
to ask the question, “why did nature choose selenium?” The
answer of the authors is that selenium must be able to perform
some chemical function necessary for biology that sulfur is not
very good at. In other words, there is a very large chemical
difference between the two elements. If the chemical differences
between selenium and sulfur were small, then nature could
abandon the use of selenium and not be dependent upon the
factors listed above and use sulfur instead. The catalytic activity
of the sulfur-containing enzyme may (or may not!) be lower
than that of the selenium-containing ortholog, but nature could
compensate by making more of the sulfur version of the
enzyme if needed. In the following sections, we review the
chemical differences between sulfur and selenium"
|
Glutathione peroxidase in supergerm infections.
|
|
|
|
|
Inhibitory effects of glutathione on dengue virus production
Reduced glutathione (GSH) is the most powerful intracellular antioxidant and also involved in viral infections.
The pathogenesis of dengue virus (DV) infection has not been completely clarified. This study
investigated the relationship between DV serotype 2 (DV2) infections and host intracellular GSH content.
Results showed infection with DV2 resulted in a decrease in intracellular GSH, which caused NF-jB activation
and increased DV2 production. Supplemental GSH significantly inhibited activation of NF-jB,
resulting in a decreased production of DV2 in HepG2 cells. Furthermore, high activity of NF-jB and
increased production of DV2 was observed in HepG2 cells treated with buthionine sulfoximine (BSO),
an inhibitor of GSH synthesis. In conclusion, DV2 infection could reduce host intracellular GSH concentration
and benefited from this process. Supplemental GSH could inhibit viral production, indicating
GSH might be valuable in the prevention and treatment of DV2 infection.
|
Selenium Deficiency Causes Flu Virus To Mutate Into More Dangerous Forms
Influenza virus that has been passed through mice deficient in the trace nutrient selenium mutates and emerges from the mice more virulent than before, a new study shows.
|
|
Electrochemistry at the Edge of Reason: Chalcogen-Based Redox Systems in Biochemistry and Drug Design
"At the same time, Cyclic Voltammetry provides access to the redox properties of various cysteine proteins and enzymes, and hence may assist in unravelling some of the remaining mysteries of the cellular thiolstat. And finally, electrochemical methods are extraordinarily powerful and useful in the characterization and ultimately also the design of redox-modulating natural products and drugs, including potential antioxidants and anticancer agents."
|
Review: The importance of selenium to human health
Margaret P Rayman
The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of
selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant
and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune
system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression
to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse
mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other
conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated
selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute
this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world,
notably in some European countries, is giving cause for concern.
|
Why 21? The significance of selenoproteins for human
health revealed by inborn errors of metabolism
Selenocysteine is the 21st proteinogenic amino acid in mammals. The human genome contains 25 genes
encoding selenoproteins, and their significance for human health is increasingly recognized through the identification
of patients with inborn errors in selenoprotein biosynthetic factors or in individual selenoproteins.Mutations
in selenoprotein N (SEPN1) lead to a spectrum of disorders collectively called SEPN1-related myopathy, and
mutations in glutathione peroxidase 4 (GPX4) cause respiratory failure and bone defects, and mutations in thioredoxin
reductase 2 (TXNRD2) are associated with familial glucocorticoid deficiency. Pathogenic mutations in
selenocysteine synthase (SEPSECS) cause neurodevelopmental disorders, but also other factors epistatic to
selenoprotein biosynthesis, such as SECIS-binding protein 2 (SECISBP2) and tRNA[Ser]Sec, are known to cause
complex disorders. Mutations in the latter 2 genes involve impaired metabolism and action of thyroid hormones
which lead to delayed bone growth and maturation. Mutations in SECISBP2 sometimes affect nervous system
development, muscle, inner ear, skin, and immune system function underlining the significance of selenoproteins
for the organism. Mouse models helped to delineate the functions of selenoproteins and explain pathomechanisms.
For brevity, this review is focused on human genetic disorders associated with selenoprotein deficiency and only
briefly touches on health effects of nutritional selenium deficiency.—
|
Selenium, ultraviolet radiation and the skin
R. C. McKenzie
Division of Dermatology, Department of Medical and Radiological Sciences, University of Edinburgh, Scotland, UK
Selenium (Se) is a dietary trace mineral in which there has recently been a surge of
interest, in both the popular and the scientific press, because of its demonstrated anticarcinogenic
and anti-inflammatory properties in humans. In this short review, I will
explain why Se is an important component of cellular anti-oxidant defenses and review
its protective effects against UV radiation-induced damage to skin cells. Although little
is known about whether selenium can protect human skin from UV-induced damage,
clinical studies are underway and the anti-oxidant may offer considerable benefits.
|
Selenium: an essential element for immune function
The importance of selenium for
optimal immune function is now
apparent. Here, Roddie McKenzie
and colleagues describe how
selenium is involved in the function
of immune cells, and the various
immune deficiencies and diseases
that result from inadequate
dietary intake.
|
|
|
