Cross-species apical microinjected selenomethionine toxicity in embryo-larval fishes.

Selenium (Se) is an essential micronutrient that becomes toxic when exposures minimally exceed those that are physiologically required. Studies on Se contaminated aquatic environments have identified that embryo-larval fishes are at particular risk of Se toxicity, primarily due to maternal Se transfer to developing eggs during oogenesis. This study emulated these exposures in embryo-larval fathead minnow (FHM), rainbow trout (RBT), white sucker (WSu), and white sturgeon (WSt) using embryonic selenomethionine (SeMet) microinjections. Adverse Se-outcomes observed across these species included spinal and edematous deformities, total individuals deformed, and reduced survival. Spinal deformity was the most sensitive sublethal endpoint and developed at the lowest concentrations in WSt (10 % effects concentration (EC10) = 12.42 µg (total) Se/g dry weight (d.w.)) followed by WSu (EC10 = 14.49 µg Se/g d.w.) and FHM (EC10 = 18.10 µg Se/g d.w.). High mortality was observed in RBT, but SeMet influences were confounded by the species' innate sensitivity to the microinjections themselves. 5 % hazardous concentrations derived across exposure type data subsets were ∼49 % higher when derived from within-species maternal transfer exclusive data as opposed to all, or within-species microinjection exclusive, data. These results support the current exclusion of SeMet microinjections during regulatory guideline derivation and their inclusion when studying mechanistic Se toxicity across phylogenetically distant fishes.

Interactive effects of fluoride and seleno-l-methionine at environmental related concentrations on zebrafish (Danio rerio) liver via the gut-liver axis.

Fluoride (F) is a ubiquitous aquatic environmental pollutant and co-exists with other pollutants to form combined pollution. Selenium (Se) is beneficial at low levels yet toxic at high levels and can interact with some metals. However, the interactive effects of F and Se on the liver in fish remains enigmatic. In this study, zebrafish (Danio rerio) were exposed to F (80 mg/L) and dietary seleno-l-methionine (Se-Met, 0.25, 0.5 and 1.0 µg/g dry weight) alone or in combination for 90 d. The results indicated that co-treatment to F and Se-Met attenuated the histopathological damage, oxidative stress, and inflammatory in the liver, compared with the F treatment alone. Meanwhile, dietary Se-Met treatment improved F-induced intestinal barrier dysfunction, increased the transcripts of tight junction proteins (ZO-1, Claudin-1 and Occludin), and restored the homeostasis of intestinal microbiota. Moreover, dietary Se-Met ameliorated F-induced intestinal and liver inflammation by inhibiting lipopolysaccharide (LPS) levels and transcripts of TLR4 and p65 in the intestine and liver. This study manifested that Se-Met alleviates F-induced liver and intestinal injury when both co-occur at specific concentrations, and that the gut-liver axis pathway may serve as a mechanistic base for these alleviative effects.

The use of selenomethionine to reduce ammonia toxicity in porcine spleen by inhibiting endoplasmic reticulum stress and autophagy mediated by oxidative stress.

Ammonia (NH3) is a typical pollutant in the atmosphere and is well known for its harmful effects on plants, animals as well as human health. Previous studies have shown that NH3 exposure can cause damage to immune organs and impaired immune function in animals. Selenomethionine is a kind of organic selenium, which can not only promote the growth and development of the body, but also inhibit the generation of intracellular reactive oxygen species (ROS), and effectively improve the immune function of the body. Therefore, this study evaluated the toxic effect of NH3 exposure on spleen from a new perspective and investigated the protective effect of selenomethionine on ammonia-induced immunotoxicity. Twenty-four Large White*Duroc*Min pigs were randomly assigned to 4 groups: control group, NH3 group, selenium group, and NH3 + selenium group. Our results showed that NH3 inhalation caused autophagy in the pig spleen, a decrease in lymphocytes, and an increase in autophagic vesicles. Also, NH3 exposure led to a decrease in the activity of some antioxidant enzymes (decreased by about 50%) and a significant increase in the expression of genes related to oxidative stress and endoplasmic reticulum stress (ERS). Our results indicated that selenomethionine mitigated ammonia toxicity in pigs (alleviated about 20-55%). In summary, our findings should be of value in providing a theoretical basis for revealing the toxicity of the high-risk gas NH3, and providing a new perspective on the mechanism of Se against toxic substances.

Protective Effect of Selenomethionine on T-2 Toxin-Induced Rabbit Immunotoxicity.

T-2 toxin is a trichothecene mycotoxin produced by fusarium species, which is mainly prevalent in grain and livestock feed. One of the main effects of this toxin is immunodepression. Previous studies have shown that T-2 toxin can cause damage to immune organs and impaired immune function in animals. However, selenomethionine (SeMet) as an organic selenium source can not only promote the growth and development of the body but also effectively improve the body's immune function. In this study, rabbits were exposed to 0.4-mg/kg T-2 toxin, and abnormal blood routine indicators were found in the rabbits. HE staining also showed obvious lesions in the spleen and thymus tissue structures, accompanied by a large number of bleeding points. In addition, rabbits showed strong oxidative stress and inflammatory response after T-2 toxin action. 0.2 mg/kg, 0.4 mg/kg, and 0.6 mg/kg organic selenium were added to the feed. However, it was found that 0.2 mg/kg selenium can effectively improve the abnormal changes of blood routine and spleen and thymus tissue of rabbits. On the other hand, it can significantly increase the expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the spleen and thymus, and downregulate the expression of reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, inflammatory factors interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood were also significantly inhibited; the expression of proliferating cell nuclear antigen (PCNA) in the spleen and thymus was also significantly increased after low-dose selenium treatment. Surprisingly, 0.4 mg/kg and 0.6 mg/kg of selenium did not effectively alleviate the immunotoxic effects caused by T-2 toxin, and cause damage to a certain extent. In summary, our results show that 0.2 mg/kg of SeMet can effectively alleviate the immunotoxicity caused by T-2 toxin. Selenium may protect rabbits from T-2 toxin by improving its antioxidant and anti-inflammatory capabilities.

Dose-dependent hepatic toxicity and oxidative stress on exposure to nano and bulk selenium in mice.

Selenium is an essential mineral naturally found in soil, water, and some of the food and is required as essential elements in human and animal body. Se supplementation is required especially for those having Se deficiency. Food supplement of selenium has several forms such as selenocysteine, selenite, selenomethionine, and selenate. Recently, Se supplement as selenium nanoparticles (SeNPs) has gained worldwide attention due to its bioactivities and properties. In the present study, we determined the potential hepatotoxicity of nano and bulk selenium using low and high doses in mice. Twenty-five Swiss albino mice (n=5) were randomly divided into 5 groups and treated orally for 28 days: Group 1: sterile saline (0.9%) as a control; Group 2: sodium selenite (1mg/kg); Group 3: sodium selenite (4mg/kg); Group 4: selenium nanoparticles (1mg/kg); and Group 5: selenium nanoparticles (4mg/kg). Administration of nano-selenium (70-90 nm) led to an increase in the activities of serum transaminases (ALT and AST), while no significant effects were noted on biochemical variables indicative of changes in heme synthesis pathway and oxidative stress like blood δ-aminolevulinic acid dehydratase (δ-ALAD), hepatic reactive oxygen species (ROS), catalase activity, superoxide dismutase (SOD), malondialdehyde assay (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) compared to controls, and a high dose of sodium selenite. Our results suggest that nano-selenium at low dose (1mg/kg) exhibited antioxidant effects in the liver compared to the high dose (4mg/kg) of SeNPs and sodium selenite (1 and 4 mg/kg). The data from the present study might be useful for pharmacologists and toxicologists in providing future directions while designing selenium-based therapeutic strategies.

Microbiota of Four Tissue Types in American Alligators (Alligator mississippiensis) Following Extended Dietary Selenomethionine Exposure.

Selenium represents an essential trace nutrient that is necessary for biological functions. Deficiencies can induce disease, but excess can induce toxicity. Selenium deficiency is a major concern in underdeveloped countries, while also posing as a toxic pollutant in waterways surrounding landfills, agricultural areas, and fossil fuel production sites. We examined the microbiome of selenomethionine (SeMet) fed American alligators (Alligator mississippiensis) at the beginning and end of a 7-week exposure experiment. Alligators were randomly divided into three groups: control and 1000 or 2000 ppm SeMet. DNA from before exposure (oral and cloaca swabs) and post-exposure (oral, cloaca, small & large intestines) sampling were extracted and amplified for bacterial 16 s rRNA. While treatment did not seem to have much effect, we observed a predominance of Fusobacteriaceae and Porpyromonodaceae across all tissue types. Cetobacterium and Clostridium are the most abundant genera as potential indicators of the aquatic and carrion feeding lifestyle of alligators.

Effects of chronic exposure to selenomethionine on social learning outcomes in zebrafish (Danio rerio): serotonergic dysregulation and oxidative stress in the brain.

For many species, social learning is crucial for fitness-related activities, but human-induced environmental changes can impair such learning processes. For instance, mining can release the element, selenium (Se), that is vital for physiological functions but also has toxicological properties at elevated concentrations. In this study, we investigated the effects of chronic exposure to Se on social learning outcomes and potential underlying molecular mechanisms in adult zebrafish. After exposure to different levels of dietary selenomethionine (control, 3.6, 12.8, 34.1 µg Se/g dry weight) for 90 days, we examined the ability of observer fish to follow demonstrators (experienced individuals) in escaping an oncoming trawl. Social learning outcomes were then assessed in the absence of demonstrators. Our results indicated that fish in the highest exposure group (34.1 µg/g) displayed significantly slower escape responses compared to fish in the control and lower exposure groups (3.6 and 12.8 µg Se/g). This impaired behavior was associated with higher oxidative stress and dysregulation in genes that are key in the serotonergic pathway, indicating that oxidative stress and alteration in the serotonergic system lead to impairment of social learning.

In ovo exposure of fathead minnow (Pimephales promelas) to selenomethionine via maternal transfer and embryo microinjection: A comparative study.

Selenium (Se) is an essential trace element of concern that is known to contaminate aquatic ecosystems as a consequence of releases from anthropogenic activities. Selenium is of particular toxicological concern for egg-laying vertebrates as they bioaccumulate Se through the diet and deposit excess Se to embryo-offspring via maternal transfer, a process which has been shown to result in significant teratogenic effects. The purpose of the present study was to determine and compare the in ovo effects of Se exposure on early development of a laboratory model fish species native to North American freshwater systems, the fathead minnow (Pimephales promelas), through two different exposure routes, maternal transfer and microinjection. For maternal transfer studies, fathead minnow breeding groups (3 females: 2 males) were exposed to diets containing Se-background levels (1.21 µg Se/g food, dry mass [dm]) or environmentally relevant concentrations of selenomethionine (SeMet; 3.88, 8.75 and 26.5 µg Se/g food dm) and bred for 28 days. Embryos were collected at different time points throughout the study to measure Se concentrations and to assess teratogenicity in embryos. While exposure to dietary Se did not negatively affect fecundity among treatment groups, the lowest treatment group (3.88 µg Se/g food dm) produced on average the most embryos per day, per female. The maternal transfer of excess Se occurred rapidly upon onset of exposure, reaching steady-state after approximately 14 days, and embryo Se concentrations increased in a dose-dependent manner. The greatest concentrations of maternally transferred Se significantly increased the total proportion of deformed embryo-larval fathead minnows but did not impact hatchability or survival. In a second study, fathead minnow embryos were injected with SeMet at concentrations of 0.00 (vehicle control), 9.73, 13.5 and 18.9 µg Se/g embryo dm. Microinjection of SeMet did not affect hatchability but significantly increased the proportion of deformed embryo-larval fish in a dose-dependent manner. There was a greater proportion of deformed fathead minnows at embryo Se concentrations of 18.9 µg Se/g embryo dm when exposed via microinjection versus maternal transfer at concentrations of 28.4 µg Se/g embryo dm. However, the findings suggest that both exposure routes induced analogous developmental toxicities in early life stage fish at Se concentrations between 9.73 and 13.5 µg Se/g embryo dm. Overall, this study demonstrated that microinjection has utility for studying the effects of Se in embryo-larval fish and is a promising method for the study of early life stage Se exposure in egg-laying vertebrates.

Effect of sub-chronic dietary L-selenomethionine exposure on reproductive performance of Red Swamp Crayfish, (Procambarus clarkii).

The effect of selenium (Se) on the reproductive system has been investigated in both humans and vertebrates, but few studies of female fertility and reproduction in invertebrate have been reported. This study is aimed to investigate the effect of SeMet on growth performance and reproductive system after crayfish were fed with graded levels of dietary SeMet (0, 1.49, 3.29, 10.02, 30.27 or 59.8 µg Se/g dry weight) for 60 days. Crayfish treated with the high levels of SeMet (10.02, 30.27 and 59.76 µg Se/g) exhibited decreasing FW and CL in both male and female. Interestingly, Se accumulation was higher in ovary than in other tissues, suggesting that ovary may serve as a target organ for Se accumulation. We found that dietary Se concentration of 10.02 µg Se/g significantly improved the spawning rate, promoted the synchronized spawning, and up-regulated the expressions of mRNA of cdc2 and vitellogenin, with significantly increased E2 and VTG concentrations in hemolymph of female crayfish. However, a marked decrease of the E2 contents and spawning rate was observed in the groups treated with 30.27 and 59.76 µg Se/g diets. In conclusion, the results of this study indicated that the Se had maximum accumulation in ovary, affecting the reproductive capacity by intervening the expression of cdc2 and vitellogenin in the reproductive system. The LOAEL to induce FW was observed in crayfish fed with 10.02 µg Se/g diet, and its value can cause toxicity within the range of natural concentration, so the addition of Se in the feed should be within 10.02 µg Se/g.

Examining the Effects of Chronic Selenium Exposure on Traditionally Used Stress Parameters in Juvenile American Alligators (Alligator mississippiensis).

Environmental contaminants, such as the trace element selenium (Se), are a continuing concern to species worldwide due to their potential pathophysiological effects, including their influence on the stress response mediated through glucocorticoids (GCs; stress hormones). Environmental concentrations of Se are increasing due to anthropogenic activities, including the incomplete combustion of coal and subsequent disposal of coal combustion wastes. However, most studies examining how Se affects GCs have been focused on lower trophic organisms. The objectives of this study were to investigate the effects of long-term Se exposure on traditionally used stress parameters and to identify which of these parameters best indicate Se accumulation in liver and kidney of the American alligator (Alligator mississippiensis), a top trophic carnivore found in the southeastern United States and known to inhabit Se-containing areas. Alligators were divided into three dietary treatments and fed prey spiked with 1000 or 2000 ppm of selenomethionine (SeMet) or deionized water (control treatment) for 7 weeks. Following the 7-week treatment protocol, blood and tissue samples were obtained to measure plasma corticosterone (CORT; the main crocodilian GC), tail scute CORT, the ratio of peripheral blood heterophils (H) to lymphocytes (L) as H/L ratio, and body condition. To evaluate which parameter best indicated Se accumulation in the liver and kidney, principal component and discriminant analyses were performed. The only parameter significantly correlated with liver and kidney Se concentrations was scute CORT. Our results suggest that measurement of CORT in tail scutes compared with plasma CORT, H/L ratios, and body condition is the best indicator of Se-exposure and accumulation in crocodilians.

Toxicity of dietary selenomethionine in juvenile steelhead trout, Oncorhynchus mykiss: tissue burden, growth performance, body composition, hematological parameters, and liver histopathology.

The steelhead trout (Oncorhynchus mykiss) is the species most at risk from selenium (Se) exposure in the San Francisco Bay Delta (SFBD). However, although steelhead trout are usually exposed to environmental Se in the juvenile stage, data to test their sensitivity to excess Se, especially its organic form, in the juvenile stage are scarce. Therefore, the objective of the current study was to assess the sensitivity of juvenile steelhead trout to ecologically relevant forms of Se using integrated sensitive endpoints. Fish (mean weight: 22.3 g) were fed one of five diets containing 1.1 (control), 8.8, 15.4, 30.8, and 61.6 µg Se/g diet dw (Se1.1, Se8.8, Se15.4, Se30.8, and Se61.6, respectively) in the form of selenomethionine for 4 weeks. After 4 weeks, Se significantly accumulated in a dose-dependent manner in all tissues at different rates. The growth rate and plasma cholesterol were significantly depressed in fish fed diets containing Se30.8 and above. Hematological parameters and mortality were significantly elevated in fish fed the Se61.6 diet. Marked histopathological alterations were observed in fish fed the Se8.8 diet (the lowest observed effect concentration, LOEC) and above. The current results suggest that the steelhead trout is more sensitive to excess Se than nonanadromous rainbow trout used in previous studies because of its lower LOEC despite the use of selenomethionine and the shorter experimental duration. Additionally, it should be noted that the current Se levels found in the SFBD are already a threat to the threatened population of steelhead trout on the central California coast.

The Effects of Selenomethionine on the Escape Behaviours of Fathead Minnows.

Selenium (Se) is an essential micronutrient for animals and yet becomes toxic with only a small increase in concentration. Toxicological studies have reported various effects of Se on fishes, including developmental impacts and deformities of the musculature and sensory systems. This paper investigates the impact of sublethal concentrations of Se on the ability of the Fathead Minnow (Pimephales promelas) to perform escape responses, a routine behaviour important to predator-prey dynamics. Predation is among the strongest evolutionary driving forces in nature. Changes to this dynamic can have effects that cascade through the ecosystem. We used responses to mechanical and visual stimuli to determine the impact of environmentally relevant concentrations of dietary selenomethionine on the behaviour of minnows. Latency to respond to the stimulus and kinematic performance were assessed. Our results indicated that there was no significant effect of selenomethionine on either the visual response to a threat or burst swimming behaviours of the fast-start response in minnows. Levels of Se in tissues approached that of tissue-specific guidelines set by regulatory bodies across North America. This suggests that current regulations are adequately protecting this key component of predator avoidance in Fathead Minnows.

Chronic exposure to dietary selenomethionine dysregulates the genes involved in serotonergic neurotransmission and alters social and antipredator behaviours in zebrafish (Danio rerio).

Selenium (Se) is a metalloid of potential interest from both a toxicological and nutritional perspective, having a range of safe intake. The adverse neuro-behavioural effects of Se have been investigated in both humans and fishes, but little is known about its effects on social behaviours or the serotonergic signaling pathway in the brain. In the present study, we investigated the effects of chorionic dietary exposure to Se (as selenomethionine) at different concentrations (control, 2.1, 11.6 or 31.5 µg/g dry wt.) on antipredator avoidance, shoaling behaviour, and social group preferences in adult zebrafish (Danio rerio). In addition, we also measured the expression of important genes in the serotonergic pathway that influence social behaviours. After 60 days of exposure, the highest dose (31.5 µg/g dry wt.) caused the highest level of baseline fear behaviour, with fish swimming lower in the water column and in tighter shoals compared to fish in the other treatments. With high levels of baseline fear, these fish did not significantly intensify fear behaviours in response to predation risk in the form of exposure to chemical alarm cues. When individual fish were given an opportunity to shoal with groups of differing sizes (3 vs. 4 individuals), fish exposed to the high dose spent less time with groups in general, and only control fish showed a significant preference for the larger group. In the zebrafish brain, we found significant upregulation in the mRNA expression of serotonin receptors (htr1aa and htr1b), a transporter (slc6a4a), and tryptophan hydroxylase-2 (tph2), whereas there was a downregulation of the monoamine oxidase (mao) gene. The results of this study suggest that disruption of serotonergic neurotransmission might have been responsible for Se-induced impairment of antipredator and social behaviour in zebrafish.

Dietary Selenomethionine Administration and Its Effects on the American Alligator (Alligator mississippiensis): Oxidative Status and Corticosterone Levels.

Selenium (Se) is an essential nutrient which in excess causes toxicity. The disposal of incompletely combusted coal, which often is rich in Se, into aquatic settling basins is increasing the risk of Se exposure worldwide. However, very few studies have looked at the physiological effects of Se exposure on long-lived, top trophic vertebrates, such as the American alligator (Alligator mississippiensis). During a 7-week period, alligators were fed one of three dietary treatments: mice injected with deionized water or mice injected with water containing 1000 or 2000 ppm selenomethionine (SeMet). One week after the last feeding alligators were bled within 3 min of capture for plasma corticosterone (CORT). A few days later, all alligators were euthanized and whole blood and tail tissue were harvested to measure oxidative damage, an antioxidant-associated transcription factor, and antioxidant enzymes [glutathione peroxidase-1 (GPX1), superoxide dismutase-1 (SOD1), and SOD2] by Western blotting. There was a dose-dependent increase in baseline CORT levels in alligators administered SeMet. Except for blood SOD2 levels, SeMet treatment had no effect (p > 0.05 for all) on oxidative status: oxidative damage, GPX1, SOD1, and muscle SOD2 levels were similar among treatments. Our results illustrate that high levels of Se may act as a stressor to crocodilians. Future studies should investigate further the physiological effects of Se accumulation in long-lived, top-trophic vertebrates.

Cardiometabolic response of juvenile rainbow trout exposed to dietary selenomethionine.

Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 µg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 µg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Previous studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can cause significant cardiotoxicity and alter aerobic metabolic capacity, energy homeostasis and swimming performance. The goal of this study aims to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular and metabolic implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in juvenile rainbow trout (Oncorhynchus mykiss). Juvenile rainbow trout were fed either control food (1.3 µg Se/g d.m.) or Se-Met spiked food (6.4, 15.8 or 47.8 µg Se/g d.m.) for 60 d at 3% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function in vivo. Chronic dietary exposure to Se-Met significantly increased stroke volume, cardiac output, and ejection fraction. Fish fed with Se-Met spiked food had elevated liver glycogen and triglyceride stores, suggesting impaired energy homeostasis. Exposure to Se-Met significantly decreased mRNA abundance of citrate synthase (CS) in liver and serpin peptidase inhibitor, clad H1 (SERPINH) in heart, and increased mRNA abundance of sarcoplasmic reticulum calcium ATPase (SERCA) and key cardiac remodelling enzyme matrix metalloproteinase 9 (MMP9) in heart. Taken together, these responses are consistent with a compensatory cardiac response to increased susceptibility to oxidative stress, namely a decrease in ventricular stiffness and improved cardiac function. These cardiac alterations in trout hearts were linked to metabolic disruption in other major metabolic tissues (liver and skeletal muscle), impaired glucose tolerance with increased levels of the toxic glucose metabolite, methylglyoxal, increased lipid peroxidation in skeletal muscle, development of cataracts and prolonged feeding behaviour, indicative of visual impairment. Therefore, although juvenile rainbow trout hearts were apparently able to functionally compensate for adverse metabolic and anti-oxidant changes after chronic dietary exposure Se-Met, complications associated with hyperglycemia in mammalian species were evident and would threaten survival of juvenile and adult fish.

Maternal dietary exposure to selenium nanoparticle led to malformation in offspring.

Selenium (Se) is an essential element and its biological activity is related to its speciation. It is also well-known that in excess it can cause teratogenesis in fish and birds. In this study we compared dietary toxicity of elemental selenium nanoparticles (SeNPs) with selenite and selenomethionine (Se-Met). Japanese medaka (Oryzias latipes) was used as a laboratory model to determine Se effects on adults and their offspring. Adult females were individually exposed using a dry diet fortified with 0, 10 or 20 µg/g of the three Se species for 7 days and then allowed to breed for 3 days. Fertilization rate and the proportion of malformed offspring were examined. The three Se diets led to significant increase in maternal tissue Se concentration in the order of Se-Met >>selenite > SeNP. However, in terms of proportion of malformed offspring, the effect of Se-Met = selenite > SeNP. The malformations included pericardial edema and craniofacial changes, which were typical for Se toxicity. The mismatch of maternal ovary Se concentration and proportion of malformed offspring suggested total Se concentration is a poor predictor of toxicity and teratogenesis. Comparing expression of four genes related to oxidative stress in maternal tissue also showed that there were significant differences in expression patterns between three Se diets in the order of selenite = SeNP > Se-Met. Our results showed that SeNPs cause similar toxicity as other Se species but require further study to elucidate the underlying mechanism.

Interactive effects of chronic dietary selenomethionine and cadmium exposure in rainbow trout (Oncorhynchus mykiss): A preliminary study.

The present study investigated the interactive effects of dietary cadmium (Cd) and selenium (Se) on the tissue-specific (liver, kidney, and muscle) accumulation of these two elements, hepatic oxidative stress response, and morphometrics in rainbow trout (Oncorhynchus mykiss) during chronic exposure. Fish were exposed to elevated dietary Cd (45 µg g-1 dry wt.), and medium (10 µg g-1 dry wt.) or high (45 µg g-1 dry wt.) dietary selenium (added as selenomethionine), both alone and in combination, for 30 days. Exposure to dietary Cd alone caused oxidative stress in fish as reflected by reduced thiol redox (GSH:GSSG), increased lipid peroxidation, and induction of anti-oxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in the liver. Also, an increase in tissue-specific Cd burden and impaired morphometrics (hepato-somatic index and condition factor) were also recorded in fish following exposure to dietary Cd. In contrast, the dietary co-exposure to Cd and Se (at both medium and high doses) resulted in a decrease in Cd burden in the liver and kidney of fish. However, co-exposure to medium, but not high, dose of dietary Se completely alleviated Cd-induced oxidative stress and impaired morphometrics in fish, indicating that the reduced Cd tissue burden might not have been the primary factor behind the amelioration of Cd toxicity by Se. Overall, our study demonstrated that the protective effect of Se against the chronic Cd toxicity in fish is mainly mediated by the anti-oxidative properties of Se, but this protective effect is dose-specific and occurs only at a moderate exposure dose.

Experimentally Induced Selenosis in Yellow-Bellied Slider Turtles ( Trachemys scripta scripta).

Selenosis, or selenium toxicosis, occurs in wildlife and livestock, usually because of excessive intake of selenium via selenium-containing plants. Although it is known that wild slider turtles can accumulate large amounts of selenium, little is known about how selenium exposure may affect these reptiles. In this study, the authors report histopathologic changes in yellow-bellied sliders ( Trachemys scripta scripta) caused by experimental exposure to selenomethionine. Microscopic changes in kidney and claw tissue were most significant and resembled those reported in birds. Turtles in the selenium treatment groups had acute tubular degeneration and regeneration in the kidney, with hyaline droplets in the high-dose animals, and changes in the claws ranging from epidermal hyperplasia with disorganization and intercellular edema to ulceration, and accumulation of seroheterophilic exudate between the epidermis and cornified layer. Although selenium burdens in this study are comparable with values found in wild slider turtles, more data are needed to determine if similar histopathologic abnormalities arise in wild animals exposed to high levels of selenium.

Chronic Dietary Selenomethionine Exposure Induces Oxidative Stress, Dopaminergic Dysfunction, and Cognitive Impairment in Adult Zebrafish (Danio rerio).

The present study was designed to investigate the effects of chronic dietary exposure to selenium (Se) on zebrafish cognition and also to elucidate possible mechanism(s) by which Se exerts its neurotoxicity. To this end, adult zebrafish were exposed to different concentrations of dietary l-selenomethionine (control, 2.3, 9.7, 32.5, or 57.7 µg Se/g dry weight) for 30 days. Cognitive performance of fish was tested using a latent learning paradigm in a complex maze. In addition, we also evaluated oxidative stress biomarkers and the expression of genes involved in dopaminergic neurotransmission in the zebrafish brain. Fish treated with higher dietary Se doses (32.5 and 57.5 µg Se/g) exhibited impaired performance in the latent learning task. The impaired learning was associated with the induction of oxidative stress and altered mRNA expression of dopamine receptors, tyrosine hydroxylase, and dopamine transporter genes in the zebrafish brain. Collectively, our results illustrate that cognitive impairment in zebrafish could be associated with Se-induced oxidative stress and altered dopaminergic neurotransmission in the brain.

Sensitivity and toxic mode of action of dietary organic and inorganic selenium in Atlantic salmon (Salmo salar).

Depending on its chemical form, selenium (Se) is a trace element with a narrow range between requirement and toxicity for most vertebrates. Traditional endpoints of Se toxicity include reduced growth, feed intake, and oxidative stress, while more recent finding describe disturbance in fatty acid synthesis as underlying toxic mechanism. To investigate overall metabolic mode of toxic action, with emphasis on lipid metabolism, a wide scope metabolomics pathway profiling was performed on Atlantic salmon (Salmo salar) (572±7g) that were fed organic and inorganic Se fortified diets. Atlantic salmon were fed a low natural background organic Se diet (0.35mg Se kg-1, wet weight (WW)) fortified with inorganic sodium selenite or organic selenomethionine-yeast (SeMet-yeast) at two levels (∼1-2 or 15mgkg-1, WW), in triplicate for 3 months. Apparent adverse effects were assessed by growth, feed intake, oxidative stress as production of thiobarbituric acid-reactive substances (TBARS) and levels of tocopherols, as well as an overall metabolomic pathway assessment. Fish fed 15mgkg-1 selenite, but not 15mgkg-1 SeMet-yeast, showed reduced feed intake, reduced growth, increased liver TBARS and reduced liver tocopherol. Main metabolic pathways significantly affected by 15mgkg-1 selenite, and to a lesser extent 15mgkg-1 SeMet-yeast, were lipid catabolism, endocannabinoids synthesis, and oxidant/glutathione metabolism. Disturbance in lipid metabolism was reflected by depressed levels of free fatty acids, monoacylglycerols and diacylglycerols as well as endocannabinoids. Specific for selenite was the significant reduction of metabolites in the S-Adenosylmethionine (SAM) pathway, indicating a use of methyl donors that could be allied with excess Se excretion. Dietary Se levels to respectively 1.1 and 2.1mgkg-1 selenite and SeMet-yeast did not affect any of the above mentioned parameters. Apparent toxic mechanisms at higher Se levels (15mgkg-1) included oxidative stress and altered lipid metabolism for both inorganic and organic Se, with higher toxicity for inorganic Se.