Selenium - Toxicology of Metals - page 770

from a selenium-rectifi er production plant, whereas
higher values were observed in a few samples from
grinding workshops (up to 3600

5.2 Selenium Defi ciency and Diseases
Related to Selenium Status
In animals, a number of well-defi ned selenium defi -
ciency diseases have been described, and several diseases
in man have been associated with relative selenium defi -
ciency (Rayman, 2000). A hypothesis that the side effects
of statins, cholesterol-lowering drugs that inhibit meval-
onate synthesis, may be due to induction of selenium
defi ciency by reducing the isopentenylation of seleno-
cysteine-tRNA has been discussed (Moosmann and Behl,
2004). Biochemical effects of experimentally induced
selenium defi ciency will be discussed in Section 5.3.3.

g/m 3 ) (Glover,
1967). Selenium fumes may contain selenium dioxide
in concentrations as high as 50% (Glover, 1970) and
are often described as the main selenium problem
in the work environment. Air levels in a plant melt-
ing selenium-containing alumina used in electronic
industries varied from 100-1000

µ

µ g/m 3 (Thomassen,

1985, personal communication).

5 BIOLOGICAL FUNCTION
AND METABOLISM

5.2.1 Animals

Defi ciency diseases have been described in many
farm animals and laboratory animals and include dys-
function of several organs and growth retardation.
Reproductive failures are seen in rodents, dogs, pigs,
monkeys, cows, and ewes. Myopathies are also seen in
a number of species, especially in ruminants. Pigs are
often affected by cardiomyopathy. Liver necrosis, hemo-
lysis, kidney degeneration, exudative diathesis, and pan-
creatic fi brosis are other important signs of defi ciency,
the latter two especially in poultry (Diplock, 1976; WHO,
1987). Experiments that used genetically manipulated
mice to obtain selenium defi ciency targeted to the liver
show that this organ is severely damaged within a few
months (Carlson et al ., 2004).

5.1 Biological Functions
Selenium is an essential trace element in many spe-
cies including man. Selenium is an integral part of fi ve
glutathione peroxidase (GSH-px1-5) enzymes and
several other proteins. The human selenoproteome
consists of 25 selenoproteins (Kryukov et al ., 2003). All
of them contain SeCys, and about half of them have
so far been ascribed a biological function (Schomburg
et al ., 2004). Bacterial selenoproteins are primarily
involved in catabolic processes, whereas mammalian
selenoproteins, as far as is known, participate in anti-
oxidant, anabolic processes (Hatfi eld and Gladyshev,
2002). Viral selenoproteins may compete for selenium
with selenoprotein synthesis in host animals (Zhao
et al ., 2000). Selenium-dependent GSH-px enzymes
protect the organism against oxidative damage by
reducing lipoperoxides and hydrogen peroxide. It has
recently been shown that homocysteine, a risk factor
of cardiovascular disease, down-regulates GSH-
px1 (Handy et al ., 2005). Interestingly, GSH-px4 may
also be converted to structural protein during sperm
maturation (Ursini et al ., 1999). Thioredoxin reduct-
ases are other selenoproteins that catalyze reduction
of oxidized cellular proteins such as thioredoxin and
may also play a role in redox regulation and resist-
ance to oxidative stress and apoptosis (Smart et al .,
2004). A third group is iodothyrodine deiodinases,
which controls the level of active triiodothyronine and
thereby thyroid hormone signaling.
Disruption of the gene for selenocysteine (SeCys)
tRNA is embryonically lethal (Bosl et al ., 1997), as
well as disruption of the GSH-px 4 gene in mouse
embryos (Yant et al ., 2003). A high reactivity of SeCys
in selenoproteins has been related to a lower pKa for
the selenol group than that for corresponding sulfhy-
dryl group of Cys. Sulfur-containing analogs of sele-
noenzymes can be orders of magnitude less effi cient
(Schomburg et al ., 2004).

5.2.2 Selenium and Cardiovascular Diseases

Keshan disease is an endemic cardiomyopathy in
children and pregnant women who live in the Keshan
region of China, where selenium levels in food are
extremely low. The incidence of the disease was
dramatically reduced when the population was supple-
mented with sodium selenite. However, a cardiotoxic
coxsackievirus or another unknown environmental
factor has also been implicated as part of the etiology
(Beck et al ., 2004; Chen, 1980). Cardiomyopathy has also
been reported in selenium-defi cient patients receiving
total parenteral nutrition; and lower serum selenium
levels have been found in patients with cardiomyopa-
thy (Johnson et al ., 1981; Oster et al ., 1983). Patients with
phenylketonuria and on a diet have very low selenium
levels, but show no signs of cardiomyopathy. Salonen
et al . (1982) showed a signifi cant inverse correlation
between serum selenium levels and cardiovascular
death in a matched-pair longitudinal study.

5.2.3 Selenium and Cancer

A large number of experiments, probably hundreds,
have been carried out to assess the effect of selenium