Page 504 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Selenium Chapter | 33 471

VetBooks.ir selenium, which are not bioavailable (Cousins and Metabolism
Cairney, 1961; Whanger et al., 1968; Peter et al., 1982).
Selenite is metabolized in red blood cells to hydrogen sele-
This reduction in bioavailability is generally exacer-
batedbyhighcarbohydratediets but can be altered by nide (Gasiewicz and Smith, 1978). Sequential methylation
reactions result in the formation of monomethylselenide,
differing rumen microbial populations (Hudman and
dimethylselenide and trimethylselenide (Kajander et al.,
Glenn, 1984; Koenig et al., 1997). Some rumen
1991; Itoh and Suzuki, 1997). These reactions utilize
microbes more efficiently reduce selenium, while others
S-adenosylmethionine for methyl groups that are transferred
effectively incorporate it into selenium-containing
by methyltransferases (Kajander et al., 1991). These sequen-
amino acids. The incorporation of selenium into micro-
tial reactions can deplete available S-adenosylmethionine,
bial proteins as well as systemic absorption, can be
which would limit the degree of methylation. In rats given
competitively inhibited by natural methionine and cyste-
selenomethionine, trimethylselenide occurred in the urine
ine (Serra et al., 1996).
more rapidly than in rats given sodium selenite or selenocys-
teine, indicating that selenomethionine may be converted to
Distribution methylselenol, which is easily further methylated.
Selenomethionine is metabolized by demethylation to
Tissue distribution is dependent on the chemical form of
selenocysteine. This set of pathways is similar to the
selenium absorbed. Selenium is generally utilized for
metabolism of methionine. The selenocysteine is then
synthesis of selenoproteins, incorporated into tissue pro-
metabolized by selenocysteine-beta-lyase in the liver and
teins or eliminated. Selenomethionine can be nonspecifi-
kidney to alanine and selenide (Soda et al., 1987).
cally incorporated into tissue proteins in place of
methionine (Awadeh et al., 1998), but selenocysteine
cannot (Burk et al., 2001), with highest incorporation Elimination
occurring in tissues with high rates of protein synthesis
(Hansson and Jacobsson, 1966). The nonspecific incor- Selenium is primarily excreted in the urine and feces, but
poration of selenomethionine effectively serves as a the form and extent of elimination by different routes are
pool of selenium reserve with a long biological half-life dose and species dependent. In monogastric animals, uri-
(Schroeder and Mitchener, 1972a). Highest total sele- nary elimination predominates, irrespective of the route of
nium content is typically found in the kidney and liver, exposure (Leng et al., 2000), with less than 10% recov-
with lesser amounts in all other tissues (Muth et al., ered in feces (Burk et al., 1972). Some literature suggests
1967; Levander, 1987; Echevarria et al., 1988; Davidson that urinary eliminated selenium is predominantly meta-
and Kennedy, 1993). Both specific and nonspecific bolites of selenium, with trimethylselenide predominating
selenium incorporation into proteins was greater in at higher doses (McConnell and Roth, 1966; Palmer et al.,
selenium-deficient animals. 1969; Zeisel et al., 1987; Itoh and Suzuki, 1997), but
Time to peak tissue concentrations is tissue dependent. monomethylselenide is more abundant at lower doses.
Peak selenium content of blood, liver, muscle, kidney, Human elimination is tri-exponential for selenite and sele-
spleen, and lung was reached within 24 h after an injec- nomethionine (Alexander et al., 1987). The terminal elim-
75
tion of Se as selenite (Muth et al., 1967). Peak serum ination phase was 8 20 and 230 days for selenite and
and blood concentrations in sheep were achieved in 12 h selenomethionine, respectively. Overall selenium reten-
or fewer for selenate, selenium from western aster, sele- tion and maintenance of adequate seleno-enzymes are for
nomethionine, and methylselenocysteine (Davis et al., much longer time periods in animals supplemented with
2011). In contrast, brain, thymus, and reproductive organs selenomethionine than selenite. Elimination rate is dose
do not reach maximal content until much later (Brown dependent, with half-lives of 19.5 and 1.2 days with sele-
and Burk, 1973; McConnell et al., 1979; Smith et al., nite of 0.1 and 1.0 ppm in the diet, respectively (Burk
1979; Behne et al., 1988). Peak hair accumulation of et al., 1972). Elimination rates in sheep also differ signifi-
selenium in poisoned steers was reached at 22 days cantly depending on the chemical form of selenium
pot-exposure (Davis et al., 2012). ingested (Davis et al., 2011). Individual tissue elimination
Selenium is efficiently transferred across the placenta rates were found to be different in steers that ingested
into feti during gestation. The overall maternal selenium selenium accumulator plants at a mine contamination site,
content is positively correlated with fetal and newborn with serum and liver having terminal elimination half-
selenium status (McConnell and Roth, 1964). Although lives of 40.5 and 38.2 days while whole blood and skele-
they get the vast majority of selenium in utero, newborns tal muscle had half-lives of 115.6 and 98.5 days (Davis
do get minimal amounts of selenium from milk, with et al., 2012). The longer elimination half-lives for whole
much higher content in colostrums than in milk later in blood and skeletal muscle likely represent red blood cell
lactation. turnover rates and protein turnover rates for muscle tissue.