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PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS

Selenium (L-Selenomethionine)

Humans and animals require selenium for the function of a number of selenium-dependent
enzymes, also known as selenoproteins. During selenoprotein synthesis, selenocysteine is
incorporated into a very specific location in the amino acid sequence in order to form a functional
protein. At least 25 selenoproteins have been identified, but the metabolic functions have been
identified for only about one-half of them. The selenoproteins with an identified function include:
glutathione peroxidises which are antioxidant enzymes (Gladyshev, 2006); thioredoxin reductase
which participates in the regeneration of several antioxidants including vitamin C (Mustacich
& Powis, 2000); iodothyronine deiodinases involved in the regulation of thyroid hormones
(Hatfield et al., 2006); selenoprotein P, associated with protection of vascular endothelial cells
against reactive nitrogen species (Arteel et al., 1999); selenoprotein W, thought to play a role in
muscle growth and differentiation by protecting the developing myoblast from oxidative stress
(Loflin et al. 2006); selenoprotein V functions in spermatogenesis; selenoprotein S is involved
with inflammatory and immune responses; kDA selenoprotein has a redox function and is
implicated in cancer prevention (Gladyshev, 2006). Animal studies indicate that selenium and
vitamin E tend to spare one another and that selenium can prevent some of the damage resulting
from vitamin E deficiency in models of oxidative stress (Sword et al., 1991). Only one paper reports
experimentally produced clinical signs of selenium deficiency in dogs; there are no reports for
cats. Clinical signs include anorexia, depression, dyspnea, and coma (NRC, 2006).

Toxicity for selenium has not been documented in dogs and cats when administered orally in therapeutic doses.
TOXICOLOGY Parenteral selenium products are also quite toxic, especially to young animals, and have caused deaths in baby
However, a single acute oral dose of selenium in the range of 1-5 mg/kg of body weight is lethal in most animals.

pigs, calves, and dogs at doses as low as 1.0 mg/kg of body weight (Kahn & Line, 2010). Oral LD for sodium
50
selenite is 1.0 mg/kg in rabbits, 3.0 mg/kg of body weight in mice and 4.8-7.0 mg/kg of body weight in rats
(EMEA, 1997). Vitamin E exhibits a protective effect on selenium intoxication (Berschneider et al., 1976).

DRUG Validated interactions studies do not exist for selenium preparations. However, the anticonvulsant
INTERACTIONS medication valproic acid has been found to decrease plasma selenium levels. Animal studies have
found that supplemental sodium selenite decreases the toxicities of the antibiotic nitrofurantoin
(Flodin, 1990).

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