title: Comparative oral dose toxicokinetics of selenium compounds commonly found in selenium accumulator plants.
abstract: Consumption of Se accumulator plants by livestock can result in Se intoxication. Recent research indicates that the Se forms most common in Se accumulator plants are selenate and Se-methylselenocysteine (MeSeCys). In this study the absorption, distribution, and elimination kinetics of Se in serum and whole blood of lambs dosed with a single oral dose of (1, 2, 3, or 4 mg Se/kg BW) of sodium selenate or MeSeCys were determined. The Se concentrations in serum and whole blood for both chemical forms of Se followed simple dose-dependent relationships. Se-methylselenocysteine was absorbed more quickly and to a greater extent in whole blood than sodium selenate, as observed by a greater peak Se concentration (Cmax; P < 0.0001), and faster time to peak concentration (Tmax; P < 0.0001) and rate of absorption (P < 0.0001). The rate of absorption and Tmax were also faster (P < 0.0001) in serum of lambs dosed with MeSeCys compared with those dosed sodium selenate at equimolar doses; however, Cmax in serum was greater (P < 0.0001) in lambs dosed with sodium selenate compared with those dosed MeSeCys at equimolar doses. The MeSeCys was absorbed 4 to 5 times faster into serum and 9 to 14 times faster into whole blood at equimolar Se doses. There were dose-dependent increases in the area under the curve (AUC) for Se in serum and whole blood of lambs dosed with both sodium selenate and MeSeCys. In whole blood the MeSeCys was approximately twice as bioavailable as sodium selenate at equimolar doses as observed by the AUC, whereas in serum there were no differences (P > 0.05) in AUC at the same doses. At 168 h postdosing the Se concentration in whole blood remained much greater (P < 0.0001) in lambs dosed with MeSeCys as compared with lambs dosed with sodium selenate; however, the serum Se concentrations were not different between treatments at the same time point. The results presented in this study demonstrate that there are differences between the kinetics of different selenocompounds when orally dosed to sheep. Therefore, in cases of acute selenosis, it is important to understand the chemical form to which an intoxicated animal was exposed when determining the importance and meaning of Se concentration in serum or whole blood obtained at various times postexposure.
authors.affiliation: USDA-ARS, Poisonous Plant Research Laboratory, Logan, Utah 84341, USA. zane.davis@ars.usda.gov
authors.forename: T Z
authors.initials: TZ
authors.lastname: Davis
authors.forename: B L
authors.initials: BL
authors.lastname: Stegelmeier
authors.forename: K D
authors.initials: KD
authors.lastname: Welch
authors.forename: J A
authors.initials: JA
authors.lastname: Pfister
authors.forename: K E
authors.initials: KE
authors.lastname: Panter
authors.forename: J O
authors.initials: JO
authors.lastname: Hall
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D064586:Selenic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017279:Selenocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D034561:Sheep, Domestic / Q000254:growth & development / Q000378:metabolism*
chemical_list: D017279:Selenocysteine; D064586:Selenic Acid; C002979:selenomethylselenocysteine