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Introduction to Toxicology
EV 460/660 & BI 460/660
Fall 2014
Alisha Moore Presentation
Selenium Toxicity in Humans
I. Discovery of Selenium
- Discovered by a Swedish chemist , Jacob Berzerlius in 1817
- Analyzed impurity contaminated with sulfuric acid
- Believed it was tellurium, but unknown element evidently recognized as selenium
II. Brief overview of Selenium properties, location, and functions
-Metalloid that serves as both a toxicological perspective and nutritional supplement,
with a very narrow safe range of intake
A. Common dietary exposures to selenium include soil, water, some foods such as
Brazil nuts, walnuts, fresh and saltwater fish (tuna, cod, red snapper, herring) ,
beet, poultry and grains
B. Non-dietary exposures to selenium
1. Low levels of air-approximately 10 ng/m3
2. Occupational exposure- metal industries, selenium-recovery processes,
painting, and special trades
C. Se protein functions and role in metabolism
1. Incorporated into proteins by co-translational mechanism as part of the amino
acid selenocysteine
 co translational- specific signal recognition pathway that delivers secretory
proteins to ER membrane while they are still being synthesized by
ribosomes
2. Involved in thyroid metabolism, spermatogenesis, Ca2+ signaling and brain function
3. Functions include antioxidant activities, biosynthesis of DNA, reduction of oxidized
proteins and membranes, redox regulation of transcription factors, regulation of
apoptosis, immunomodulation, and regulator of thyroid hormones, selenium transport
storage, protein folding and degradation
III. Normal ranges of selenium in serum
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Dietary intake: 0.04 ppm
Accumulation in biological tissue
Adult concentration in serum: 70-150ng/ ml
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Children require lower concentrations
Optimal selenium concentrations are age dependent
Toxic levels exceed 4ppm
IV. Excess dietary selenium concentrations may negatively impact physiological systems
- Examples include: thyroid metabolism, cardiovascular health, neurological
system, and immunological responses
V. Importance of Selenium in the Immune System
A. Function
1. Plays important role in inflammation and immunity
2. Regulate excessive immune responses and chronic inflammation
3. Influence leukocyte effector functions
4. Regulates immune cell signaling and function
VI. Toxic Effects on the Immune System (Immunotoxicity)
A. Impacts of Deficient Selenium concentrations
1. Interferes with immune system during activation, differentiation, and
proliferation
2. Increases oxidative stress
3. Impairs protein folding and calcium influx
4. Negatively affects immune cell function
5. Increases susceptibility to pathogens and diseases
VII.
Effects of Selenium toxicity in thyroid metabolism
A. Brief review of thyroid properties
1. Thyroid hormone synthesized by thyroid via iodination of tyrosine residues in
the glycoprotein thyroglobulin
2. Thyroid hormone essential for normal development, growth, neural
differentiation, and metabolic regulation in mammals
3. Regulates broad range of genes after its activation from T4 to the active form
T3
4. TSH secreted by anterior pituitary in response to circulating thyroid hormone,
acts directly on the TSH receptor symporter
5. Thyroid deficiencies lead to maternal iodine deficiency, untreated congenital
hypothyroidism, neurological deficits, growth retardation
6. Thyroid hormones are modulators of the immune response
B. Importance of selenium to thyroid system
1. Essential for thyroid metabolism
2. Antioxidant properties which protect thyroid gland from oxidative stress
3. Prevents myoxedematous cretinism and autoimmune disease
4. Protects thyroid gland from oxidative damage
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VIII.
Deficiency selenium concentrations leads to toxic effects on thyroid organ
1. Decreased selenium levels correlates with risk of goiter and multiple nodules in
European women
2. Selenium deficient individuals are more likely to have disturbed immune systemthyroid interaction
3. Aggravates manifestation of myxedematous cretinism and autoimmune thyroid
disease
4. Prevents selenoproteins such as glutathione peroxidase from inhibiting apoptosis
process
Study Guide Questions
1. If you consume excess amounts of selenium, will it weaken the immune system? If so,
how?
2. Does selenium alleviate inflammatory diseases such as arthritis?
3. Since selenium plays an important role in thyroid metabolism, will decreased level of
selenium concentrations cause weight gain?
4. Briefly describe the impacts of deficient selenium concentrations on the immune system.