Selenocompounds in juvenile white sturgeon: estimating absorption, disposition, and elimination of selenium using Bayesian hierarchical modeling

Abstract

The biological function of selenium (Se) is determined by its form and concentration. Selenium is an essential micronutrient for all vertebrates, however, at environmental levels, it is a potent toxin. In the San Francisco Bay-Delta, Se pollution threatens top predatory fish, including white sturgeon. A multi-compartmental Bayesian hierarchical model was developed to estimate the fractional rates of absorption, disposition, and elimination of selenocompounds, in white sturgeon, from tissue measurements obtained in a previous study (Huang et al., 2012). This modeling methodology allows for a population based approach to estimate kinetic physiological parameters in white sturgeon. Briefly, thirty juvenile white sturgeon (five per treatment) were orally intubated with a control (no selenium) or a single dose of Se (500 μg Se/kg body weight) in the form of one inorganic (Selenite) or four organic selenocompounds: selenocystine (SeCys), l-selenomethionine (SeMet), Se-methylseleno-l-cysteine (MSeCys), or selenoyeast (SeYeast). Blood and urine Se were measured at intervals throughout the 48h post intubation period and eight tissues were sampled at 48 h. The model is composed of four state variables, conceptually the gut (Q1), blood (Q2), and tissue (Q3); and urine (Q0), all in units of μg Se. Six kinetics parameters were estimated: the fractional rates [1/h] of absorption, tissue disposition, tissue release, and urinary elimination (k12, k23, k32, and k20), the proportion of the absorbed dose eliminated through the urine (f20), and the distribution blood volume (V; percent body weight, BW). The parameter k12 was higher in sturgeon given the organic Se forms, in the descending order of MSeCys > SeMet > SeCys > Selenite > SeYeast. The parameters k23 and k32 followed similar patterns, and f20 was lowest in fish given MSeCys. Selenium form did not affect k20 or V. The parameter differences observed can be attributed to the different mechanisms of transmucosal transport, metabolic reduction, and storage of the Se forms, which, in general, appear to be similar to that in mammals. We have demonstrated that the Bayesian approach is a powerful tool for integrating quantitative information from a study with sparse blood and urinary measurements and tissue concentrations from a single time point, while providing a full characterization of parameter variability. The model permits the quantitative mechanistic interpretation and predictions of Se absorption, disposition, and elimination processes. Furthermore, the model represents a first step towards population based physiological toxicokinetic modeling of Se in white sturgeon.