Effects of chronic exposure to dietary selenomethionine on the physiological stress response in juvenile white sturgeon (Acipenser transmontanus).

Selenium (Se) is an essential micronutrient, but at low concentrations can be toxic to aquatic organisms. Selenomethionine (SeMeth) is the primary dietary form of Se aquatic organisms are exposed to and is an environmental concern because it persists and bioaccumulates. White sturgeon (WS) might be particularly susceptible to bioaccumulative toxicants, such as SeMeth, due to their longevity and benthic lifestyle. Se exposure is known to have adverse effects on the physiological stress response in teleosts, but these effects are unknown in WS. Therefore, the goal of this study was to determine effects of dietary SeMeth on the ability of WS to mount a stress response. Juvenile WS were administered food spiked with 1.4, 5.6, 22.4 and 104.4µg Se/g dry mass (dm) for 72days. Lower doses were chosen to represent environmentally relevant concentrations, while the high dose represented a worst case scenario exposure. On day 72, fish were subjected to a 2min handling stressor, and they were sampled at 0, 2 and 24h post-stressor. Cortisol, glucose and lactate concentrations were quantified in blood plasma and glycogen concentrations were quantified in muscle and liver. Transcript abundance of genes involved in corticosteroidogenesis and energy metabolism were determined using qPCR. Under basal conditions, WS fed 104.4µg Se/g dm had significantly greater concentrations of plasma cortisol and lactate, and significantly lower concentrations of plasma glucose and liver glycogen, compared to controls. Corticosteroid 11-beta dehydrogenase 2 (hsd11b2) abundance was lower in WS fed 22.4 and 104.4µg Se/g dm, indicating less conversion of cortisol to cortisone. Abundance of the glucocorticoid receptor (gcr) was significantly lower in high dose WS, suggesting lower tissue sensitivity to glucocorticoids. The increasing trend in phosphoenolpyruvate carboxykinase (pepck) abundance, with increasing SeMeth exposure, was consistent with greater cortisol and glucose concentrations in high dose WS. Exposure to an acute handling stressor elicited a typical cortisol response, but the magnitude of the response appeared to be significantly lower than those typically observed in teleosts. SeMeth also did not appear to modulate the cortisol response to a secondary stressor. However, WS exposed to 22.4µg Se/g dm and sampled 2h post-stressor, had significantly higher concentrations of muscle glycogen compared to controls, indicating effects on their ability to utilize muscle glycogen for energy. Overall, the results indicate that chronic exposure to dietary SeMeth concentrations >22.4µg/g can affect cortisol dynamics and mobilization of energy substrates in juvenile WS.

Is hepatic oxidative stress a main driver of dietary selenium toxicity in white sturgeon (Acipenser transmontanus)?

Most species of sturgeon have experienced significant population declines and poor recruitment over the past decades, leading many, including white sturgeon (Acipenser transmontanus), to be listed as endangered. Reasons for these declines are not yet fully understood but benthic lifestyle, longevity, and delayed sexual maturation likely render sturgeon particularly susceptible to factors such as habitat alteration and contaminant exposures. One contaminant of particular concern to white sturgeon is selenium (Se), especially in its more bioavailable form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in prey items of this species. Studies have shown white sturgeon to be among the most sensitive species of fish to dietary SeMet as well as other pollutants such as metals, dioxin-like chemicals and endocrine disrupters. One of the primary hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress; however, little is know about the specific mode by which SeMet affects the health of white sturgeon. Therefore, the aim of this study was to characterize oxidative stress and associated antioxidant responses as a molecular event of toxicity, and to link it with the pathological effects observed previously. Specifically, three-year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4 or 104.4µg Se per g feed (dm). Doses were chosen to range over a necessary Se intake level, current environmentally relevant intakes and an intake representing predicted increases of Se release. Lipid hydroperoxides, which are end products of lipid oxidation, were quantified as a marker of oxidative stress. Changes in gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3 were quantified as markers of the response to oxidative stress. Concentrations of lipid hydroperoxides were highly variable within dose groups and no dose response was observed. GPx expression was significantly increased in the low dose group indicating an induced antioxidant response. Expression of other genes were not significantly induced or suppressed. Overall, there was very little evidence of oxidative stress, and therefore, in contrast to previous reports on other species of teleost fishes, oxidative stress is not believed to be a main driver of toxicity in white sturgeon exposed to SeMet.

Adverse health effects and histological changes in white sturgeon (Acipenser transmontanus) exposed to dietary selenomethionine.

It has been shown that selenium (Se) released to the aquatic environment can have devastating effects on local wildlife. White sturgeon (Acipenser transmontanus) have a life history particularly susceptible to contaminants, and their protection is of interest as they are culturally and economically important, and many populations are classified as endangered. During the present 72-d dietary study, multiple signs of decreased health and Se lethality were observed. Juvenile white sturgeon were given diets containing 1.4 µg, 5.6 µg, 22.4 µg, or 104.4 µg selenomethionine/g food (dry mass). Selenium accumulated in muscle and liver tissue in a dose-dependent manner. Edema causing exophthalmos developed within 15 d and 23 d, and lethal effects occurred in 54% and 22% of fish in the high- and medium-dose groups, respectively. Growth and hepatosomatic index were significantly lower in the high-dose group, which also had a high incidence of food avoidance. Histology of the liver revealed a dose-dependent increase in melanomacrophage aggregates and decrease of energy stores, which indicated toxicity. These results indicate that white sturgeon are susceptible to the effects of Se accumulation over relatively short time periods. This stresses the need for continued sturgeon research and studies looking into the environmental fate and regulation of released Se. Environ Toxicol Chem 2016;35:1741-1750. © 2015 SETAC.

Seeking perfection in healthcare. A case study in adopting Toyota Production System methods.

Virginia Mason Health System's vision to be the quality leader in healthcare means continually adopting new ways of thinking. One change has been shifting from believing defects are to be expected to believing zero defects in healthcare is not only possible, but also necessary. Generally, healthcare has advanced in technology and understanding of disease, but its business and management systems have changed little since the 1950s. Virginia Mason realized it needed a management method to help make real and measurable improvements in safety, quality, service and staff satisfaction.