Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VI. Selenium
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of Se deficiency on immunocompetence are recognized,
the biochemical lesions underlying these effects have not
been delineated. Anemia appears to involve a depression
in GPx activity and subsequent Heinz body formation
( Arthur, 1998 ; Koenig et al. , 1997 ; Smith et al. , 1987 ;
Spears, 2000 ).
In humans, Keshan disease is an endemic congestive
cardiomyopathy affecting primarily children and women
of childbearing age with lesions that are very similar to the
characteristic lesions of nutritional cardiomyopathy associated
with white muscle disease ( Burk and Hill, 2005 ). The
disease derives its name from a serious outbreak of the disorder
in the Keshan province of Northern China in 1935.
That Se supplementation improves many of the clinical
signs of Keshan’s disease identifies it as a Se-responsive
disorder. The soils of the Keshan area are low in Se as
well as locally produced produce. Another human disorder
is Keshan-Beck disease, an endemic osteoarthropathy
that occurs in several regions of eastern Asia. The disease
is characterized by chronic, disabling, degenerative osteoarthrosis
and frequently occurs in young children. In the
initial phase, the patient complains of general limb weakness
and joint stiffness. With progression, the disease
results in shortening of the fingers and long bones with
severe enlargement and dysfunction of the joints. Although
other aspects of the etiology of the disease have not been
defined, it has been suggested that Se deficiency can be a
principal underlying cause.
2 . Se and Viral Infections
The study of Keshan disease also has led to an association
between Se and increased susceptibility to infection with
certain enteroviruses. The discovery that the cardiomyopathy
of Keshan disease likely had a dual etiology (nutritional
and infectious) provided impetus for additional studies of
relationships between nutritional Se status and viral infection.
Observed was that an amyocarditic strain of coxsackievirus
B3, CVB3/0, was converted to a highly virulent
strain when it was inoculated into Se-deficient mice. This
conversion was accompanied by changes in the genetic
structure of the virus so that its genome closely resembled
that of other known virulent CVB3 strains. Similar alterations
in virulence and genomic composition of CVB3/0
could be observed in mice fed normal diets but genetically
deprived of GPx (e.g., the use of knockout mouse models;
Beck, 2007 ). In addition, more recent observations have
shown that two strains of influenzavirus exhibit increased
virulence when given to Se-deficient mice. Again, this
increased virulence is accompanied by multiple changes
in the viral genome in a segment previously thought to be
relatively stable. Ongoing research should resolve many
of the mechanistic details. Important herein is the concept
that there is a basis for linking the expression of viral diseases
to nutrition ( Beck, 2007 ).
3 . Se Toxicity
Three types of Se toxicity have been identified in livestock:
acute and chronic blind staggers and chronic alkali disease
(Subcommittee on Mineral Toxicity in Animals, 1980).
Abnormal movement and posture, breathing difficulties,
diarrhea, and rapid death characterize acute Se toxicity.
Chronic Se toxicity of the blind staggers type occurs when
animals consume Se toxic accumulator plants (usually over
a period of weeks or months). They develop blindness,
severe abdominal pain, and paralysis. Death often results
from respiratory failure.
Se toxicity of the alkali disease type occurs when animals
consume high Se diets (5 to 50 microgram/m; 0.063
to 0.63 micromol/g) for prolonged periods of time. Alkali
disease is characterized by emaciation, a lack of vitality,
cardiac atrophy, erosions of the joints of the long bones,
hepatic cirrhosis, and anemia (Subcommittee on Mineral
Toxicity in Animals, 1980). Se has also been reported to
affect normal development of the embryo and fetus in cattle,
pigs, and sheep following consumption of seleniferous
diets, and Se toxicity has been shown to induce malformations
and reduce hatching success, growth, and survival of
young in poultry, quail, and mallards ( Hamilton, 2004 ).
In the high Se areas of Wyoming, South Dakota, and
Nebraska in the United States, human Se toxicosis was
suggested to be a problem, but this has not been substantiated
and is less of concern now that foods are available
from around the world rather than a local region. Endemic
Se toxicity has also been reported in the Hubei province of
China. The selenosis has been linked to high Se contamination
of the soil. It has been estimated that affected individuals
can have consumed 5 mg Se/day (63.3 micromol/day)
or more for several years. Signs of toxicity included hair
loss in the early stages and, in the later stages, convulsions,
paralysis, and motor disturbances. Human intakes throughout
most of the world are between 20 and 300 microgram
Se/day (0.25 to 3.80 micromol/day) and other large animals
perhaps two to three times that amount ( Burk and
Hill, 2005 ).
E . Evaluation of Selenium Status
Because deficiency-related disorders are more common
than selenosis (Se toxicity), most laboratories assess Se
adequacy indirectly by measurement of erythrocyte GPx
activity or selenoprotein P ( Reilly, 2004 ). Plasma GPx
measurements can also be used as an index of Se status.
Plasma GPx levels, however, can be affected by erythrocyte
GPx leakage. Erythrocyte GPx activity is 25 to 100
times higher than plasma GPx activity so that even minor
hemolysis negates the value of plasma GPx.
Although most commonly used, the sole use of GPx
is often questioned given the wide tissue variation in GPx
activity that is storage dependent, reflecting the adequacy