Reproductive and Developmental Effects of Sex-Specific Chronic Exposure to Dietary Arsenic in Zebrafish (Danio rerio).

The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), and 100 (high) µg/g dry weight, as arsenite] for 90 days. Following exposure, arsenic-exposed females from each dietary treatment were mated with control males, and similarly, arsenic-exposed males from each dietary treatment were mated with control females. In females, arsenic exposure resulted in a dose-dependent decrease in reproductive performance (fecundity, fertilization success, and hatching success). Moreover, a dose-dependent increase in developmental toxicity (larval deformities and larval mortality) was observed with maternal exposure to arsenic. In contrast, in males, arsenic exposure also induced similar reproductive and developmental toxicity; however, the adverse effects were mainly evident only in the medium and high dietary arsenic treatment groups. We also examined the sex-specific effects of dietary arsenic exposure on the expression of genes that regulate the hypothalamus-pituitary-gonadal-liver (HPG-L) axis in fish. The gene expression results indicated the downregulation of HPG-L axis genes in females irrespective of the arsenic treatment dose; however, the reduced expression of HPG-L axis genes in males was recorded only in the medium and high arsenic treatment groups. These observations suggest that chronic arsenic exposure in either females or males causes reproductive and developmental toxicity in zebrafish. However, these toxic effects are markedly higher in females than in males. Our results also suggest that arsenic can act as an endocrine disruptor and mediate reproductive and developmental toxicity by disrupting the HPG-L axis in zebrafish.

Maternal exposure to bisphenol S reduces anxiety and impairs collective antipredator behavior of male zebrafish (Danio rerio) offspring through dysregulation of their serotonergic system.

Bisphenol S (BPS) is a common endocrine-disrupting chemical globally used in several consumer and industrial products. Although previous studies suggested that BPS induces multiple effects in exposed organisms, very little is known about its intergenerational effect on offspring behavior and/or the potential underlying mechanisms. To this end, adult female zebrafish Danio rerio were exposed to BPS (0, 10, 30 µg/L) and 1 µg/L of 17-ß-estradiol (E2) as a positive control for 60 days. Afterwards, female fish were bred with untreated males, and their offspring were raised to 6 months old in control water. Maternal exposure to BPS decreased male offspring anxiety and antipredator behaviors while boldness remained unaffected. Specifically, maternal exposure to 10 and 30 µg/L BPS and 1 µg/L E2 were found to impact male offspring anxiety levels as they decreased the total time that individuals spent in the dark zone in the light/dark box test and increased the total track length in the center of the open field test. In addition, maternal exposure to all concentrations of BPS and E2 disrupted antipredator responses of male offspring by decreasing shoal cohesion in the presence of chemical alarm cues derived from conspecifics, which communicated high risk. To elucidate the possible molecular mechanism underlying these neuro-behavioral effects of BPS, we assessed the serotonergic system via changes in mRNA expression of serotonin receptors, including the 5-HT1A, 5-HT1B, and 5-HT1D subtypes, the serotonin transporter and monoamine oxidase (MAO). The impaired anxiety and antipredator responses were associated with reduced levels of 5-HT1A subtype and MAO mRNA expression within the brain of adult male offspring. Collectively, the results of this study demonstrate that maternal exposure to environmental concentrations of BPS can interfere with the serotonergic signaling pathway in the developing brain, subsequently leading to the onset of a suite of behavioral deficits in adult offspring.

Oral arsenite exposure induces inflammation and apoptosis in pulmonary tissue: acute and chronic evaluation in young and adult mice.

Inorganic arsenic is a well-known environmental toxicant, and exposure to this metalloid is strongly linked with severe and extensive toxic effects in various organs including the lungs. In the present study, we aimed to investigate the acute and chronic effects of arsenite exposure on pulmonary tissue in young and adult mice. In brief, young and adult female Balb/C mice were exposed to 3 and 30 ppm arsenite daily via drinking water for 30 and 90 days. Subsequently, the animals were sacrificed and various histological and immunohistochemistry (IHC) analyses were performed using lung tissues. Our findings showed arsenite was found to cause dose-dependent pathological changes such as thickening of the alveolar septum, inflammatory cell infiltrations and lung fibrosis in young and adult mice. In addition, arsenite exposure significantly increased the expression of inflammatory markers NF-κB and TNF-α, indicating that arsenite-exposed mice suffered from severe lung inflammation. Moreover, the IHC analysis of fibrotic proteins demonstrated an increased expression of TGF-ß1, α-SMA, vimentin and collagen-I in the arsenite-exposed mice compared to the control mice. This was accompanied by apoptosis, which was indicated by the upregulated expression of caspase-3 in arsenite-exposed mice compared to the control. Adult mice were generally found to be more prone to arsenite toxicity during chronic exposure relative to their younger counterparts. Overall, our findings suggest that arsenite in drinking water may induce dose-dependent and age-dependent structural and functional impairment in the lungs through elevating inflammation and fibrotic proteins.

Examining the subchronic (28-day) effects of aqueous Cd-BaP co-exposure on detoxification capacity and cardiac function in adult zebrafish (Danio rerio).

The present study aimed to examine the effects of environmentally relevant concentrations of cadmium (Cd) and Benzo[a]Pyrene (BaP) in the adult zebrafish (Danio rerio). To this end, fish were exposed to either 1 or 10 µg/L Cd or 0.1 or 1 µg/L BaP in isolation, or a co-exposure containing a mixture of the two toxicants. Our results showed extensive modulation of the expression of key antioxidant genes (GPx, SOD1, catalase), detoxifying genes (MT1, MT2, CYP1A1) and a stress biomarker (HSP70) differing between control, single toxicant groups and co-exposure groups. We additionally carried out histopathological analysis of the gills, liver, and hearts of exposed animals, noting no differences in tissue necrosis or apoptosis. Finally, we carried out ultrasonographic analysis of cardiac function, noting a significant decrease of E-wave peak velocity and end diastolic volume in exposed fish. This in turn was accompanied by a decrease in stroke volume and ejection fraction, but not cardiac output in co-exposed fish. The present study is the first to demonstrate that a subchronic aqueous exposure to a Cd-BaP mixture can extensively modulate detoxification capacity and cardiac function in adult zebrafish in a tissue-specific manner.

Chronic dietary exposure to arsenic at environmentally relevant concentrations impairs cognitive performance in adult zebrafish (Danio rerio) via oxidative stress and dopaminergic dysfunction.

The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 µg/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 µg/g dw) and high (100 µg/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2_mg, entpd2_mq, and 5'-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxidative stress and disrupting the dopaminergic neurotransmission in the brain.

Investigating the combined effects of pH changes and UV radiation exposure on dissolved metal-humate complexes: an important process in aquatic systems.

An in vitro study was carried out to examine the impact of UV exposure on metal-dissolved humic material (M-DHM) complexes in aqueous systems at different pH. Complexation reactions of dissolved M (Cu, Ni, and Cd) with DHM increased with the increasing pH of the solution. Kinetically inert M-DHM complexes dominated at higher pH in the test solutions. Exposure to UV radiation did affect the chemical speciation of M-DHM complexes at different pH of the systems. The overall observation suggests that exposure to increasing UV radiation increased the lability, mobility, and bioavailability of M-DHM complexes in aquatic environments. The dissociation rate constant of Cu-DHM was found to be slower than Ni-DHM and Cd-DHM complexes (both before and after UV exposure). At a higher pH range, Cd-DHM complexes dissociated after exposure to UV radiation and a part of this dissociated Cd precipitated out from the system. No change in the lability of the produced Cu-DHM and Ni-DHM complexes after UV radiation exposure was observed. They did not appear to form new kinetically inert complexes even after 12 h of exposure. The outcome of this research has important global implications. The results of this study helped to understand DHM leachability from soil and its effect on dissolved metal concentrations in the Northern Hemisphere water bodies. The results of this study also facilitated to comprehend the fate of M-DHM complexes at photic depths (where pH changes are accompanied by high UV radiation exposure) in tropical marine/freshwater systems during summer.

Arsenic causing gallbladder cancer disease in Bihar.

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples-gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.

Modulation of Cd and BaP uptake rate during acute aqueous co-exposure in adult zebrafish (Danio rerio).

Cadmium and Benzo[a]pyrene are two toxicants of great environmental importance given their frequency and ability to cause extensive toxicity in aquatic organisms including fish. There is evidence that fish can modulate their respective uptake rate during simultaneous exposures, albeit the mechanism behind this is poorly understood. The present study aimed to examine this interaction by exposing adult zebrafish to either 89.3 nM Cd, 4.25 nM BaP or a combination of the two for 72 hrs prior to examining the uptake rate of either toxicant via short-term exposures (3-6 hrs) to radiotracers (109Cd and 14C-BaP). Our results showed that Cd uptake rate increased significantly in the gills when animals were pre-exposed to both toxicants simultaneously, resulting in an increased maximum uptake rate (Jmax). The increased Cd uptake rate did not correspond to increased expression of gill Cd transporters such as the epithelium calcium channel (ECaC) or the divalent metal transporter 1 (DMT1). Furthermore, BaP uptake rate increased significantly at the whole-body level when animals were exposed to both 5.03 nM 14C-BaP and 89.3 nM Cd concurrently. Additionally, we ran a time-course and observed BaP uptake rate is highest in the 6-12 hrs following the beginning of the exposure. Our results provide evidence that the increased bioaccumulation of Cd and BaP observed during co-exposures is at least in part due to an increase in uptake rate and is driven by separate mechanisms.

Melatonin Attenuates Extracellular Matrix Accumulation and Cardiac Injury Manifested by Copper.

Copper-induced cardiac injury is not widely reported in spite of its ability to cause oxidative damage and tissue injury. Structural and morphological changes in the cardiac tissue are triggered via oxidative stress and inflammatory responses following copper exposure. The varied and unavoidable exposure of copper through contaminated food and water warrants a safe and effective agent against its harmful effects. Since the heart is highly sensitive to changes in the redox balance, the present study was undertaken to examine the protective effects of melatonin against copper-induced cardiac injury. Sprague Dawley (SD) rats were exposed to 100 ppm of elemental copper via drinking water for 4 months. The cardiac tissue was evaluated for various biochemical, histological, and protein expression studies. Animals exposed to copper exhibited induced oxidative stress and cardiac injury compared to normal control. To this end, we found that melatonin treatment ameliorated copper-induced alterations in tissue oxidative variables like ROS, nitrate, MDA, and GSH. In addition, histological examinations unravelled decreased cardiac muscle dilation, atrophy, and cardiomyopathy in melatonin-treated rats. Furthermore, melatonin-treated rats were associated with reduced tissue copper levels, collagen deposition, α-SMA, and increased HO-1 expression as compared to rats exposed exclusively to copper. Moreover, the levels of NF-κB and cardiac markers such as CK-MB, cTnI, and cTnT were found to be decreased in the melatonin-treated animals. Altogether, melatonin-triggered increase in antioxidant capacity resulting in reduced aggregation of ECM components demonstrates the therapeutic potential of melatonin in the treatment of cardiac injury and tissue fibrosis.

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention.

Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.

Maternal exposure to bisphenol S induces neuropeptide signaling dysfunction and oxidative stress in the brain, and abnormal social behaviors in zebrafish (Danio rerio) offspring.

Recent studies show that bisphenol S (BPS) induces multiple adverse effects in exposed organisms; however, the maternal effects of BPS exposure remain poorly understood. Here, we expose adult female zebrafish to environmentally relevant concentrations of BPS (0, 1, 10, 30 µg/L) and 1 µg/L of 17-ß-estradiol (E2) as a positive control for 60 days. Females were then paired with BPS-unexposed males and their offspring were raised in control water for 6 months. Maternal exposure to BPS was found to alter social behavior and anxiety response in a dose-specific manner in male offspring. Group preferences and social cohesion were significantly reduced by maternal exposure to 1 and 10 µg/L BPS, respectively. Additionally, maternal exposure to 1 and 30 µg/L BPS and E2 decreased offspring stress responses during the novel tank test. The impaired social behavior was associated with elevated arginine-vasotocin (AVT) level as well as with the altered expression of genes involved in AVT signaling pathway (AVT, avpr1aa) and enzymatic antioxidant genes (cat and Mn-sod) in the brain. Collectively, these results suggest that maternal exposure to environmentally relevant concentrations of BPS alters social behavior in zebrafish offspring, which is likely mediated by oxidative stress and disruption of neuropeptide signaling pathways in the brain.

Proximate causes and ultimate effects of common antidepressants, fluoxetine and venlafaxine, on fish behavior.

Antidepressant (AD) drugs are widely prescribed for the treatment of psychiatric disorders, including depression and anxiety disorders. The continuous use of ADs causes significant quantities of these bioactive chemicals to enter the aquatic ecosystems mainly through wastewater effluent discharge. This may result in many aquatic organisms being inadvertently affected by these drugs. Fluoxetine (FLX) and venlafaxine (VEN) are currently among the most widely detected ADs in aquatic systems. A growing body of experimental evidence demonstrates that FLX and VEN have a substantial capacity to induce neurotoxicity and cause behavioral dysfunctions in a wide range of teleost species. At the same time, these studies often report seemingly contradictory results that are confounding in nature. Hence, we clearly require comprehensive reviews that attempt to find overarching patterns and establish possible causes for these variable results. This review aims to explore the current state of knowledge regarding the neurobehavioral effects of FLX and VEN on fishes. This study also discusses the potential mechanistic linkage between the neurotoxicity of ADs and behavioral dysfunction and identifies key knowledge gaps and areas for future research.

Predictive biomarkers of cardiovascular disease in adult Canadian population.

BACKGROUND: Elevated levels of the enzymes gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and C-reactive protein (CRP) have been shown to be associated with increased risk of cardiovascular disease (CVD). Objective: To assess cross-sectional relationships between biomarkers GGT, ALT, AST, ALP and CVD in adult Canadian population. METHODS: The Canadian Health Measures Surveys (CHMSs) are a series of cross-sectional national surveys and collect information on indicators of general health and wellness of Canadians. The CHMS has four components. We used data from the first three components (for Study participants ≥ 20 years) from CHMS cycles 1 through 5. RESULTS: Multivariable logistic regression revealed: immigration status [Odds ratio (OR)(95% Confidence Interval (95% CI)) = 0.67 (0.53-0.85), reference category (RC)-no-immigrant] education [1.38(1.10-1.75), RC- > secondary education]; smoking status [ex-smokers: 1.16(0.89-1.51); current smokers: 1.41(0.98-2.05), RC-non-smoker]; and income [middle income: 0.69(0.43-1.10); high income: 0.49(0.29-0.83); RC-lower income] were significantly associated with CVD prevalence. CONCLUSION: The relationship of GGT with CVD prevalence changed among age groups and body mass index categories; was different for males and females; and diabetes was an effect modifier in the relationship between AST and CVD prevalence. Socio-economic factors were significantly associated with CVD prevalence.

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions.

Arsenic is a key environmental toxicant having significant impacts on human health. Millions of people in developing countries such as Bangladesh, Mexico, Taiwan, and India are affected by arsenic contamination through groundwater. Environmental contamination of arsenic leads to leads to various types of cancers, coronary and neurological ailments in human. There are several sources of arsenic exposure such as drinking water, diet, wood preservatives, smoking, air and cosmetics, while, drinking water is the most explored route. Inorganic arsenic exhibits higher levels of toxicity compared its organic forms. Exposure to inorganic arsenic is known to cause major neurological effects such as cytotoxicity, chromosomal aberration, damage to cellular DNA and genotoxicity. On the other hand, long-term exposure to arsenic may cause neurobehavioral effects in the juvenile stage, which may have detrimental effects in the later stages of life. Thus, it is important to understand the toxicology and underlying molecular mechanism of arsenic which will help to mitigate its detrimental effects. The present review focuses on the epidemiology, and the toxic mechanisms responsible for arsenic induced neurobehavioral diseases, including strategies for its management from water, community and household premises. The review also provides a critical analysis of epigenetic and transgenerational modifications, mitochondrial oxidative stress, molecular mechanisms of arsenic-induced oxidative stress, and neuronal dysfunction.

Using zebrafish as a model to assess the individual and combined effects of sub-lethal waterborne and dietary zinc exposure during development.

The present research used zebrafish (5-28 days post-fertilization; dpf) as a model organism to investigate the effects of chronic exposure to environmentally relevant sub-lethal concentrations of waterborne (261 µg/L) and dietary zinc (Zn) (1500 mg Zn/kg dw), either independently or simultaneously, during development. The results showed that whole body contents of Zn were increased in all Zn treatment groups, with the highest accumulation of Zn observed in larvae simultaneously exposed to elevated waterborne and dietary Zn. In addition, exposure to elevated levels of Zn, either through the water or the diet, led to a decrease in whole body calcium (Ca) contents at 28 dpf. The findings also suggested that exposure to elevated levels of Zn resulted in a significant reduction in whole body manganese (Mn) contents. More importantly, the magnitude of decrease in Mn contents by Zn exposure was markedly higher than that in Ca and appeared to mirror the increases in whole body Zn accumulation. These results indicate that Mn regulation is more sensitive than Ca to disruption by Zn exposure in developing fish. Further examination of the Zrt-Irt-Like Protein (ZIP) family of transporters using droplet digital PCR technologies revealed that several zip transporters exhibited temporal and exposure route-specific changes following Zn exposure. In particular, the level of zip4 was influenced by Zn exposure regardless of the exposure routes, while changes in zip7 and zip8 levels were predominantly driven by waterborne exposure. Overall, our findings demonstrated that zebrafish during the developmental periods are sensitive to elevated levels of Zn seen in the environment, particularly following co-exposures to waterborne and dietary Zn. Future toxicological assessment of elevated Zn exposure should consider both the exposure routes and the life stages of fish.

Transgenerational effects of selenomethionine on behaviour, social cognition, and the expression of genes in the serotonergic pathway in zebrafish.

Elevated levels of contaminants from human activities have become a major threat to animals, particularly within aquatic ecosystems. Selenium (Se) is a naturally occurring element with a narrow range of safe intake, but excessive Se has toxicological effects, as it can bioaccumulate and cause cognitive and behavioural impairments. In this study, we investigated whether exposure to Se would also have transgenerational effects, causing changes in the descendants of exposed individuals. We exposed adult female zebrafish to either a control diet or environmentally relevant concentrations of dietary Se-Met (3.6, 12.8, 34.1 µg Se/g dry weight) for 90 days. Then, females from each treatment group were bred with untreated males, and the offspring (F1-generation) were raised to adulthood (6 months old) without Se exposure. In behavioural tests, offspring that were maternally exposed to 34.1 µg Se/g showed signs of elevated stress, weaker group preferences, and impaired social learning. Maternal exposure to high levels of Se-Met also led to dysregulation of the serotonergic system via changes in mRNA expression of serotonin receptors, including the 5-HT1A, 5-HT1B, and 5-HT1D subtypes, the serotonin transporter, and monoamine oxidase (MAO). Such perturbations in the serotonergic system, thus, appear to underlie the neurobehavioural deficits that we observed. These findings suggest that Se contamination can have important transgenerational consequences on social behaviour and cognition.

A comprehensive review on the neuropathophysiology of selenium.

As an essential micronutrient, selenium (Se) exerts its biological function as a catalytic entity in a variety of enzymes. From a toxicological perspective, however, Se can become extremely toxic at concentrations slightly above its nutritional levels. Over the last few decades, there has been a growing level of concern worldwide regarding the adverse effects of both inorganic and organic Se compounds on a broad spectrum of neurological functions. A wealth of evidence has shown that exposure to excess Se may compromise the normal functioning of various key proteins, neurotransmitter systems (the glutamatergic, dopaminergic, serotonergic, and cholinergic systems), and signaling molecules involved in the control and regulation of cognitive, behavioral, and neuroendocrine functions. Elevated Se exposure has also been suspected to be a risk factor for the development of several neurodegenerative and neuropsychiatric diseases. Nonetheless, despite the various deleterious effects of excess Se on the central nervous system (CNS), Se neurotoxicity and negative behavioral outcomes are still disregarded at the expense of its beneficial health effects. This review focuses on the current state of knowledge regarding the neurobehavioral effects of Se and discusses its potential mode of action on different aspects of the central and peripheral nervous systems. This review also provides a brief history of Se discovery and uses, its physicochemical properties, biological roles in the CNS, environmental occurrence, and toxicity. We also review potential links between exposure to different forms of Se compounds and aberrant neurobehavioral functions in humans and animals, and identify key knowledge gaps and hypotheses for future research.

Chronic exposure to bisphenol S induces oxidative stress, abnormal anxiety, and fear responses in adult zebrafish (Danio rerio).

Bisphenol S (BPS) is increasingly used in a wide range of industrial and consumer products, resulting in its ubiquitous distribution across the environment, including aquatic ecosystems. Although it is commonly known as a weak/moderate estrogenic compound, there has been a growing acknowledgment of the potential of BPS to cause toxicity by inducing oxidative stress. Oxidative stress is a major participant in the development of anxiety-like behaviors in humans and animals. Therefore, the present study was designed to examine the impact of BPS on anxiety-like behavior and fear responses in adult zebrafish and also to elucidate the possible linkage between the BPS neurotoxicity and oxidative status of the brain. To this end, adult male and female zebrafish were exposed to 0 (control), 1, 10, and 30 µg/L of BPS and 1 µg/L of 17-ß-estradiol (E2) for 75 days. Following exposure, changes in anxiety and fear-related responses were evaluated by applying a novel tank test and by exposing focal fish to chemical alarm cues. Additionally, we evaluated the expression of multiple antioxidant genes in the zebrafish brain. Our results indicate that BPS, irrespective of exposure concentration, and E2 significantly decreased bottom-dwelling behavior and the latency to enter the upper water column. Furthermore, exposure to the highest concentration of BPS and E2 induced a significant decrease in fear-related responses. The impaired anxiety and reduced fear-related responses were associated with a down-regulation in the transcription of genes involved in enzymatic antioxidant defense. Taken together, our results suggest that chronic exposure to BPS impairs anxiety and fear responses in adult zebrafish, possibly by inducing oxidative stress in the brain.

Interactive effects of cadmium and Benzo[a]pyrene in adult zebrafish (Danio rerio) during short-term aqueous co-exposure.

Environmental water quality guidelines often work under the assumption that the toxicity of environmental pollutants is identical when present in isolation or in a complex chemical mixture. Thus, there is a crucial gap in our knowledge regarding how these toxicants interact and alter the toxicological effects in aquatic organisms. The present study examined the effects of acute (72-hr) aqueous exposures of Cadmium (Cd), a highly toxic non-essential trace metal, and Benzo[a]Pyrene (B[a]P), a prototypical polycyclic aromatic hydrocarbon (PAH) in adult zebrafish. Following a range-finding series of individual single-toxicant exposures, a second series was carried out using select concentrations in binary mixture exposures (using 5.8 or 22 µg/L for Cd; 0.44 or 1.07 µg/L for B[a]P). Our results demonstrated that tissue accumulation of both toxicants increased significantly in the presence of the second toxicant relative to single-toxicant exposures. Cd-only and B[a]P-only single toxicant exposures caused a significant downregulation of cytochrome p4501a (CYP1A1) and metallothionein-2 (MT2) mRNA in the gills, respectively, however binary co-exposures using both toxicants resulted in strong up-regulation of CYP1A1 and MT2. Additionally, co-exposures caused a strong induction of SOD1 and CAT mRNA transcript levels in the gill. The observed increase in body burden and transcript modulation did not translate into additive or more-than-additive toxic effects (oxidative stress) in zebrafish.

Differences in the subcellular distribution of cadmium and copper in the gills and liver of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss).

Recent studies have shown that white sturgeon (Acipenser transmontanus) are more resistant to cadmium (Cd) compared to rainbow trout (Oncorhynchus mykiss), whereas they are more sensitive than rainbow trout when exposed to copper (Cu). Differences in the subcellular distribution of metals among species could be one of the factors responsible for the differences in the sensitivity to metals. Although, subcellular distribution has been studied extensively in many species with many metals, its direct role in species-specific differences in the sensitivity has not been well studied. The objective of this study was to evaluate the role of subcellular distribution of metals in species-specific differences in the sensitivity to metals between sturgeon and trout. We compared the subcellular distribution of metals Cd and Cu in the cellular debris, heat-stable proteins, heat-denatured fraction, metal-rich granules, and organelles fractions from the gills and liver after exposure of juveniles of both species to 1.25 and 20 µg/L Cd and Cu for 8 days, respectively. Sturgeon diverted a higher amount of Cd towards biologically inactive metal pool (BIM) and a lower amount towards the biologically active metal pool (BAM) compared to trout in both tissues. This explained why sturgeon are able to tolerate a relatively higher exposure level to Cd compared to trout. For Cu, there was no statistically significant species-specific differences in the amounts diverted towards either BAM or BIM; hence, white sturgeon's greater sensitivity to Cu was not explained by its subcellular distribution strategies.