Inferred inactivation of the Cftr gene in the duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its potential role in Cr(VI)-induced carcinogenesis of the small intestines.

Carcinogenicity of hexavalent chromium [Cr (VI)] has been supported by a number of epidemiological and animal studies; however, its carcinogenic mode of action is still incompletely understood. To identify mechanisms involved in cancer development, we analyzed gene expression data from duodena of mice exposed to Cr(VI) in drinking water. This analysis included (i) identification of upstream regulatory molecules that are likely responsible for the observed gene expression changes, (ii) identification of annotated gene expression data from public repositories that correlate with gene expression changes in duodena of Cr(VI)-exposed mice, and (iii) identification of hallmark and oncogenic signature gene sets relevant to these data. We identified the inactivated CFTR gene among the top scoring upstream regulators, and found positive correlations between the expression data from duodena of Cr(VI)-exposed mice and other datasets in public repositories associated with the inactivation of the CFTR gene. In addition, we found enrichment of signatures for oncogenic signaling, sustained cell proliferation, impaired apoptosis and tissue remodeling. Results of our computational study support the tumor-suppressor role of the CFTR gene. Furthermore, our results support human relevance of the Cr(VI)-mediated carcinogenesis observed in the small intestines of exposed mice and suggest possible groups that may be more vulnerable to the adverse outcomes associated with the inactivation of CFTR by hexavalent chromium or other agents. Lastly, our findings predict, for the first time, the role of CFTR inactivation in chemical carcinogenesis and expand the range of plausible mechanisms that may be operative in Cr(VI)-mediated carcinogenesis of intestinal and possibly other tissues.

Multi-Systemic Alterations by Chronic Exposure to a Low Dose of Bisphenol A in Drinking Water: Effects on Inflammation and NAD+-Dependent Deacetylase Sirtuin1 in Lactating and Weaned Rats.

Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 µg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (Sirt1-AS LncRNA) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period.

Evaluation of the hair cell regeneration and claudin b and phoenix gene expression during exposure to low concentrations of cadmium and zinc in early developing zebrafish larvae.

Zebrafish possess hair cells on the body surface similar to that of mammals inner hear, in particular in the neuromasts, and due to its ability in regenerating damaged hair cells, is regularly used as a powerful animal model to study in vivo cytotoxicity. Among the factors leading to hair cell disruption, metal ions are of particular concern since they are important environmental pollutants. To date, several studies on zebrafish hair cell regeneration after metal exposure exist, while no data on regeneration during continuous metal exposure are available. In the present study, neuromast hair cell disruption and regeneration were assessed in zebrafish larvae for the first time during zinc (Zn) and cadmium (Cd) continuous exposure and a visual and molecular approach was adopted. Fluorescent vital dye DASPEI was used to assess hair cell regeneration and the gene expression of claudin b (cldnb) and phoenix (pho), was analyzed. Metallotionein-2 (mt2) gene expression was used as standard molecular marker of metal toxicity and confirmed the higher toxicity of Cd compared to Zn. In addition, Cd caused a delay in hair cell regeneration compared to Zn. Molecular analysis showed cldnb gene expression increased in relation to the metal concentrations used, confirming the involvement of this gene in hair cell regeneration. On the contrary, a dramatic decrease of pho gene expression was observed in Cd exposed groups, suggesting a negative impact of Cd on pho expression, thus negatively interfering with hair cell regeneration in zebrafish larvae exposed to this metal.

Morphometric, hematological and oxidative stress changes in Clarias gariepinus following sub-chronic exposure to tramadol.

Tramadol is among the most famous analgesic drugs used for the management, treatment and relief of moderate to severe pain conditions. The present study investigated the effects of tramadol on the behavior, mortality, morphometric, hematology and oxidative stress parameters of C. gariepinus juveniles. The 96 h LC50 value of tramadol determined by probit analysis was 88.76 mg/L. Based on this value, fish were exposed to sublethal concentrations of 4.44, 8.88, 17.75 mg/L tramadol and 0.0 mg/L (control) for the period of 15 days and allowed to recover for 5 days. Fish exposed to tramadol showed some abnormal behavioral responses and mortality increased with increase in the exposure duration and concentrations except for the control. There were variations in hepatosomatic index (HSI) and condition factor (CF) in fish exposed to tramadol. Exposure of C. gariepinus to tramadol elicited reduction in the values of white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), packed cell volume (PCV) and mean corpuscular volume (MCV) while the values of mean corpuscular hemoglobin (MCH) and the mean corpuscular hemoglobin concentration (MCHC) increased. The values of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), reduced glutathione (GSH) and lipid peroxidation (LPO) increased significantly in the exposed fish compared with the control. The values of glutathione peroxidase (GPx) however decreased. The results of the present study demonstrate that tramadol is toxic to fish and its use should be monitored in the aquatic environment.

Quantification of the inflammatory responses to pro-and anti-inflammatory agents in Manila clam, Ruditapes philippinarum.

Inflammation is a form of innate immune response of living organisms to harmful stimuli. In marine bivalves, inflammation is a common defense mechanism. Several studies have investigated the morphological features of inflammation in bivalves, such as hemocyte infiltration. However, the molecular and biochemical responses associated with inflammation in marine bivalves remain unexplored. Here, we investigated changes in nitric oxide (NO) levels, cyclooxygenase 2 (COX-2) activity, and allograft inflammatory factor-1 (AIF-1) gene expression levels in hemolymph samples collected from Manila clam (Ruditapes philippinarum) exposed to pro- and anti-inflammatory substances. These included the pro-inflammatory agent lipopolysaccharide (LPS), and the nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac, all widely used in vertebrates. Our study showed that NO levels, COX-2 activity, and AIF-1 expression increased in response to the treatments with LPS and decreased in response to the treatments with NSAIDs in a concentration-dependent manner. These results suggest that the mechanism of inflammatory responses in bivalves is very similar to that of vertebrates, and we propose that inflammatory responses can be quantified using these techniques and used to determine the physiological status of marine bivalves exposed to biotic or abiotic stresses.

Low-Dose Copper Exposure Exacerbates Depression-Like Behavior in ApoE4 Transgenic Mice.

Depression is one of the most common neuropsychiatric disorders. Although the pathogenesis of depression is still unknown, environmental risk factors and genetics are implicated. Copper (Cu), a cofactor of multiple enzymes, is involved in regulating depression-related processes. Depressed patients carrying the apolipoprotein ε4 allele display more severe depressive symptoms, indicating that ApoE4 is closely associated with an increased risk of depression. The study explored the effect of low-dose Cu exposure and ApoE4 on depression-like behavior of mice and further investigates the possible mechanisms. The ApoE4 mice and wild-type (WT) mice were treated with 0.13 ppm CuCl2 for 4 months. After the treatment, ApoE4 mice displayed obvious depression-like behavior compared with the WT mice, and Cu exposure further exacerbated the depression-like behavior of ApoE4 mice. There was no significant difference in anxiety behavior and memory behavior. Proteomic analysis revealed that the differentially expressed proteins between Cu-exposed and nonexposed ApoE4 mice were mainly involved in the Ras signaling pathway, protein export, axon guidance, serotonergic synapse, GABAergic synapse, and dopaminergic synapse. Among these differentially expressed proteins, immune response and synaptic function are highly correlated. Representative protein expression changes are quantified by western blot, showing consistent results as determined by proteomic analysis. Hippocampal astrocytes and microglia were increased in Cu-exposed ApoE4 mice, suggesting that neuroglial cells played an important role in the pathogenesis of depression. Taken together, our study demonstrated that Cu exposure exacerbates depression-like behavior of ApoE4 mice and the mechanisms may involve the dysregulation of synaptic function and immune response and overactivation of neuroinflammation.

Essential concepts for interpreting the dose-response of low-level arsenic exposure in epidemiological studies.

Scientifically robust selections of epidemiological studies and assessments of the dose-response of inorganic arsenic in the low-dose range must consider key issues specific to arsenic in order to reduce risk of bias. The abundance of toxicological, mechanistic, and epidemiological evidence on arsenic enables a nuanced assessment of risk of bias in epidemiological studies of low-level arsenic, as opposed to a generic evaluation based only on standard principles. Important concepts in this context include 1) arsenic metabolism and mode of action for toxicity and carcinogenicity; 2) effects of confounding factors such as diet, health status including nutritional deficiencies, use of tobacco and other substances, and body composition; 3) strengths and limitations of various metrics for assessing relevant exposures consistent with the mode of action; and 4) the potential for bias in the positive direction for the observed dose-response relationship as exposure increases in the low-dose range. As an example, evaluation of a recent dose-response modeling using eight epidemiological studies of inorganic arsenic and bladder cancer demonstrated that the pooled risk estimate was markedly affected by the single study that was ranked as having a high risk of bias, based on the above factors. The other seven studies were also affected by these factors to varying, albeit lesser, degrees that can influence the apparent dose-response in the low-dose range (i.e., drinking water concentration of 65 µg/L or dose of approximately ≤1 µg/kg-day). These issues are relevant considerations for assessing health risks of oral exposures to inorganic arsenic in the U.S. population, and setting evidence-based regulatory limits to protect human health.

A review of low-dose arsenic risks and human cancers.

The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and "J-shaped" linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.

Bayesian benchmark dose analysis for inorganic arsenic in drinking water associated with bladder and lung cancer using epidemiological data.

Abundant epidemiological evidence has shown that there is a strong causal relationship between long-term exposure to inorganic arsenic (iAs) through drinking water and a few types of cancer (e.g., lung and bladder cancer). Traditionally, a linear low-dose extrapolation assumption was applied in risk assessment for iAs which resulted in a relatively conservative cancer risk estimate. Growing biological evidence suggests that the mode of action of iAs-induced cancer follows a threshold process (e.g., sufficient concentration of trivalent arsenic is required to disrupt normal cellular function). In this study, we applied the benchmark dose (BMD) methodology to model the relationship between the relative risk of bladder and lung cancer and the iAs concentration in drinking water using the high-quality epidemiological data reported in recently published papers, with a special focus on the low exposure range (i.e., <150 µg/L). Because of its biological plausibility and statistical flexibility, the Hill model has been chosen to model the data under a Bayesian framework. A Bayesian hierarchal model together with a bootstrap method for exposure estimation were applied to quantify uncertainty from various sources, including the within-study, between-study, and exposure uncertainties. Dose-response assessment results obtained from a number of alternative model structures and methods consistently demonstrate a threshold type dose-response curve with a threshold in the range between 40-60 µg/L of iAs concentration in drinking water. The BMD for iAs in drinking water associated with 0.1 % increase in relative risk of bladder cancer is 42.2 µg/L (BMDL 39.2 µg/L); for 0.05 % increase, the BMD is 41.6 µg/L (BMDL 38.6 µg/L). For lung cancer, the two counterpart BMD estimates are 57.0 µg/L (BMDL 43.6 µg/L) and 55.7 µg/L (BMDL 42.5 µg/L) for 0.1 % and 0.05 % increase, respectively. These analyses provide additional statistical support for a non-linear dose response for cancer risk from inorganic arsenic which may have important policy implications.

Histopathological changes and antioxidant responses in common carp (Cyprinus carpio) exposed to copper nanoparticles.

Despite the rapid increase of nanotechnology in a wide array of industrial sectors, the biosafety profile of nanomaterials remains undefined. The accelerated use of nanomaterials has increased the potential discharge of nanomaterials into the environment in different ways. The aquatic environment is mainly susceptible as it is likely to act as an ultimate sink for all contaminants. Therefore, this study assessed the toxicological impacts of waterborne engineered copper nanoparticles (Cu-NPs) on histology, lipid peroxidation (LPO), catalase (CAT), and glutathione (GSH) levels in the gills of common carp (Cyprinus carpio). Nanoparticles were characterized by XRD and SEM techniques. Before starting the sub-acute toxicity testing, 96 h LC50 of Cu-NPs for C. carpio was calculated as 4.44 mg/l. Then based on LC50, C. carpio of 40-45 g in weight were exposed to three sub-lethal doses of waterborne engineered Cu-NPs (0 or 0.5 or 1 or 1.5 mg/l) for a period of 14 days. The waterborne Cu-NPs have appeared to induce alterations in gill histology and oxidative stress parameters in a dose-dependent manner. The gill tissues showed degenerative secondary lamellae, necrotic lamella, fused lamella, necrosis of the primary and secondary lamella, edema, complete degeneration, epithelial lifting, degenerative epithelium, and hyperplasia in a dose-dependent manner. In the gill tissues, waterborne Cu-NPs caused a decreased level of CAT and elevated levels of LPO, and GSH in the fish exposed to the highest dose of 1.5 mg Cu-NPs/l of water. Our results indicate that the exposure to waterborne Cu-NPs was toxic to the aquatic organisms as shown by the oxidative stresses and histological alterations in C. carpio, a freshwater fish of good economic value.

Organophosphorus-based chemical additives induced behavioral changes in zebrafish (Danio rerio): Swimming activity is a sensitive stress indicator.

Organophosphorus flame retardants (OPFRs) have been extensively used as chemical additives in polymer based consumer products. Among them, Isopropylphenyl phosphate (IPPP) and tripropyl phosphate (TPP) are predominant, which have potential to cause neuro-toxic effects on non-target organisms. As behavior (swimming activity) response is the first adjustment due to neurotoxic stress on the fitness of fish. In this study, the quantified swimming activity of zebrafish (Danio rerio) under IPPP and TPP exposure in an online monitoring system was investigated to assess the neurotoxin effects under long-term exposure periods, no swimming anomalies were observed in the control group. Whereas, in the OPFR exposures ((treatment I: 5 µg/L and treatment II: 25 µg/L), a series of anomalies were identified. Hyperactivity was shown in IPPP treatment I group (5 µg/L), whereas zebrafish swimming activity was declined throughout the study period in IPPP treatment II (25 µg/L), and TPP groups (5 µg/L and 25 µg/L) when compared to the control group. Circadian rhythm was not affected in the present study. The results of the present study indicated that the fitness of test individuals was a valid biomarker for eco-toxicity assessment under unescapable conditions. Hypoactivity of zebrafish signified the neurotoxic effects of IPPP and TPP. A concentration based improvement in swimming activity was observed under recovery conditions, which suggested that recovery capacity along with toxicity responses could be a comprehensive non-invasive technique to assess the eco-toxicity of waterborne chemicals.

Environmental level of the antidepressant venlafaxine induces behavioral disorders through cortisol in zebrafish larvae (Danio rerio).

Psychoactive drugs discharged into the environment have different effects on the behavior of vertebrates. The objective of this study was to evaluate the effect of venlafaxine on the behavior of zebrafish, and whether melatonin could reverse the induction of venlafaxine. In this study, a series of venlafaxine concentrations (1 µg/L, 10 µg/L, 100 µg/L) was used to treat zebrafish embryos from 2 hours post-fertilization (hpf) to 5dpf. We found that venlafaxine (1 µg/L) can stimulate the growth of the head area, eye area, and body length of zebrafish. The light-dark test showed that venlafaxine (1 µg/L) could increase the activity of zebrafish larvae. What's more, venlafaxine (1 µg/L) upregulated the expression of steroid regulatory factors including steroidogenic acute regulatory protein (star), cytochrome P450 family member 11A1 (cyp11a1) and 11 ß hydroxylase (cyp11b1) by cAMP-pCREB pathway, affecting the function of the steroidogenic cells, which might be involved in the increased cortisol levels in zebrafish larvae. Whereas, melatonin (230 µg/L) restored the altered locomotion behavior induced by venlafaxine and recovered the altered gene expression. Our results demonstrate that venlafaxine at levels detected in the aquatic environment impacts behavior and may compromise the adaptive responses to the environment in zebrafish larvae.

DNA damage and health effects in juvenile haddock (Melanogrammus aeglefinus) exposed to PAHs associated with oil-polluted sediment or produced water.

The research objective was to study the presence of DNA damages in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: 1) extracts of oil produced water (PW), dominated by 2-ring PAHs; 2) distillation fractions of crude oil (representing oil-based drilling mud), dominated by 3-ring PAHs; 3) heavy pyrogenic PAHs, mixture of 4/5/6-ring PAHs. The biological effect of the different PAH sources was studied by feeding juvenile haddock with low doses of PAHs (0.3-0.7 mg PAH/kg fish/day) for two months, followed by a two-months recovery. In addition to the oral exposure, a group of fish was exposed to 12 single compounds of PAHs (4/5/6-ring) via intraperitoneal injection. The main endpoint was the analysis of hepatic and intestinal DNA adducts. In addition, PAH burden in liver, bile metabolites, gene and protein expression of CYP1A, GST activity, lipid peroxidation, skeletal deformities and histopathology of livers were evaluated. Juvenile haddock responded quickly to both intraperitoneal injection and oral exposure of 4/5/6-ring PAHs. High levels of DNA adducts were detected in livers three days after the dose of the single compound exposure. Fish had also high levels of DNA adducts in liver after being fed with extracts dominated by 2-ring PAHs (a PW exposure scenario) and 3-ring PAHs (simulating an oil exposure scenario). Elevated levels of DNA adducts were observed in the liver of all exposed groups after the 2 months of recovery. High levels of DNA adduct were found also in the intestines of individuals exposed to oil or heavy PAHs, but not in the PW or control groups. This suggests that the intestinal barrier is very important for detoxification of orally exposures of PAHs.

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps.

Accumulation, contents of protein, non-enzymatic antioxidant glutathione (GSH and GSSG), lipid peroxidation product (melondialdehyde-MDA) and organic acids (fumarate, succinate, malate and citrate), and activities of neurological (acetylcholinesterase-AChE), detoxification (glutathione S-transferase-GST) and metabolic (lactate dehydrogenase-LDH, aspartate transaminase-AST and alanine transaminase-ALT) enzymes were recorded in the hatchlings of Cyprinus carpio, Ctenopharyngodon idella, Labeo rohita and Cirrhinus mrigala after 7 and 14 days exposure and 10 days post exposure (recovery period) to sublethal concentrations (0.005, 0.01, 0.02 and 0.05 mg/L) of triclosan, a highly toxic and persistent biocide used in personal care products. Accumulation was maximum between 7-14 days at 0.01 mg/L for C. carpio and L. rohita but at 0.005 mg/L for C. idella and C. mrigala. No triclosan was observed at 0.005 mg/L in C. carpio and C. mrigala after recovery. Significant decline in protein, glutathione and acetylcholinesterase but increase in glutathione S-transferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, melondialdehyde and organic acids over control during exposure continued till the end of recovery period. Integrated biomarker response (IBR) analysis depicted higher star plot area for glutathione and glutathione S-transferase during initial 7 days of exposure, thereafter, during 7-14 days of exposure and the recovery period, higher star plot area was observed for acetylcholinesterase, aspartate transaminase, alanine transaminase and organic acids. Higher star plot area was observed for protein in all the species throughout the study. The study shows that L. rohita is most sensitive and glutathione, acetylcholinesterase, aspartate transaminase and alanine transaminase are the biomarkers for the toxicity of sublethal concentrations of TCS.

Multiple stressors in multiple species: Effects of different RDX soil concentrations and differential water-resourcing on RDX fate, plant health, and plant survival.

Response to simultaneous stressors is an important facet of plant ecology and land management. In a greenhouse trial, we studied how eight plant species responded to single and combined effects of three soil concentrations of the phytotoxic munitions constituent RDX and two levels of water-resourcing. In an outdoor trial, we studied the effects of high RDX soil concentration and two levels of water-resourcing in three plant species. Multiple endpoints related to RDX fate, plant health, and plant survival were evaluated in both trials. Starting RDX concentration was the most frequent factor influencing all endpoints. Water-resourcing also had significant impacts, but in fewer cases. For most endpoints, significant interaction effects between RDX concentration and water-resourcing were observed for some species and treatments. Main and interaction effects were typically variable (significant in one treatment, but not in another; associated with increasing endpoint values for one treatment and/or with decreasing endpoint values in another). This complexity has implications for understanding how RDX and water-availability combine to impact plants, as well as for applications like phytoremediation. As an additional product of these greenhouse and outdoor trials, three plants native or naturalized within the southeastern United States were identified as promising species for further study as in situ phytoremediation resources. Plumbago auriculata exhibited relatively strong and markedly consistent among-treatment mean proportional reductions in soil RDX concentrations (112% and 2.5% of the means of corresponding values observed within other species). Likewise, across all treatments, Salvia coccinea exhibited distinctively low variance in mean leaf chlorophyll content index levels (6.5% of the means of corresponding values observed within other species). Both species also exhibited mean wilting and chlorosis levels that were 66% and 35%, and 67% and 84%, of corresponding values observed in all other plants, respectively. Ruellia caroliniensis exhibited at least 43% higher mean survival across all treatments than any other test species in outdoor trials, despite exhibiting similar RDX uptake and bioconcentration levels.

Unexpected Observations: Probiotic Administration Greatly Aggravates the Reproductive Toxicity of Perfluorobutanesulfonate in Zebrafish.

The present study exposed adult zebrafish to 0, 10, and 100 µg/L perfluorobutanesulfonate (PFBS) with or without dietary supplement of probiotic Lactobacillus rhamnosus. Interaction between probiotic and PFBS on sex endocrine and reproduction was investigated. It was striking to find that PFBS and probiotic coexposures almost ceased the fecundity, which was accompanied by disturbances in sex hormones and oocyte maturation in females. In contrast, probiotic additive efficiently antagonized the estrogenic activity of PFBS in males. For the first time, this study reported that probiotic heavily depended on sex to modulate the endocrine disruption and reproductive toxicity of aquatic pollutants.

Chronic exposure to environmentally relevant levels of simvastatin disrupts zebrafish brain gene signaling involved in energy metabolism.

Simvastatin (SIM), a hypocholesterolaemic drug belonging to the statins group, is a widely prescribed pharmaceutical for prevention of cardiovascular diseases. Several studies showed that lipophilic statins, as SIM, cross the blood-brain barrier and interfere with the energy metabolism of the central nervous system in humans and mammalian models. In fish and other aquatic organisms, the effects of SIM on the brain energy metabolism are unknown, particularly following exposure to low environmentally relevant concentrations. Therefore, the present study aimed at investigating the influence of SIM on gene signaling pathways involved in brain energy metabolism of adult zebrafish (Danio rerio) following chronic exposure (90 days) to environmentally relevant SIM concentrations ranging from 8 ng/L to 1000 ng/L. Real-time PCR was used to determine the transcript levels of several genes involved in different pathways of the brain energy metabolism (glut1b, gapdh, acadm, accα, fasn, idh3a, cox4i1, and cox5aa). The findings here reported integrated well with ecological and biochemical responses obtained in a parallel study. Data demonstrated that SIM modulates transcription of key genes involved in the mitochondrial electron transport chain, in glucose transport and metabolism, in fatty acid synthesis and ß-oxidation. Further, SIM exposure led to a sex-dependent transcription profile for some of the studied genes. Overall, the present study demonstrated, for the first time, that SIM modulates gene regulation of key pathways involved in the energy metabolism in fish brain at environmentally relevant concentrations.

Effects of TiO2 nanoparticles on the life-table parameters, antioxidant indices, and swimming speed of the freshwater rotifer Brachionus calyciflorus.

Titanium dioxide nanoparticles (nTiO2 ) have raised environmental concerns and display potential hazards to aquatic organisms and even humans. However, only a few reports tested the toxicity of nTiO2 to rotifers. In the present study, acute and chronic toxicity of nTiO2 to the freshwater rotifer Brachionus calyciflorus was investigated at different temperatures. At 25°C, the 24 and 48-hr LC50 was 117.14 and 60.11 mg/L, respectively. At 15°C, 20°C, 25°C, and 30°C, exposure to nTiO2 significantly decreased life expectancy at birth, net reproductive rate, generation time, average lifespan, and/or intrinsic rate of population increase of B. calyciflorus (p < .05). High temperature enhanced the toxicity of nTiO2 to rotifers. The swimming linear speed of rotifers significantly increased (p < .05) in treatments with 200 µg/L nTiO2 , compared with the control. In addition, treatments with 8 µg/L to 5 mg/L nTiO2 significantly increased superoxide dismutase activity (p < .05). Glutathione content and catalase activity increased significantly after exposure to 8 µg/L nTiO2  but decreased significantly in treatments with nTiO2 concentrations ranging from 40 µg/L to 5 mg/L (p < .05). There were no significant changes in malondialdehyde contents among nTiO2 treatments and control. Overall, the present study indicated that nTiO2 revealed high toxicity to rotifers, displaying high environmental risks to aquatic ecosystems.

Sodium Fluoride and Fluoride Contaminated Ground Water Induced Altered Reproductive Performances in Male Rats.

Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)- and fluoride (F)-contaminated ground water on reproductive performances of male rats. Healthy adult male rats were categorised into three groups, first group of rats were served as control, whereas second group of rats were orally intubated with NaF (10 mg/kgbw/1 ml/rat) and third group of rats were allowed to drink F-contaminated ground water (5 mg/L) through drinking water bottles for 52 days. Exposure of NaF- and F-contaminated ground water caused significant decline in sperm motility, serum concentration of testosterone, and increase in sperm abnormality compared with controls. Further, significant histological alterations characterized with shrunken seminiferous tubules and degeneration of different stages of spermatogonial cells were observed in rats treated with NaF- and F-contaminated ground water. After the confirmation of toxic effect of F, these NaF- and F-contaminated ground water-treated male rats were allowed to mate with proven fertile untreated female rats to study the reproductive performances of male rats. There was a decline in parturition index, fertility index of male and female, gestation index and number of pups delivered in NaF-treated male rats compared with controls. However, gestation index and number of pups delivered were declined in F-contaminated ground water-treated male rats compared with controls. These results clearly indicate that F exposure affected the reproductive performances of male rats. The present study further revealed the fact that F-induced decline in testosterone levels, reduced sperm motility, and loss of spermatogonial cells affected the reproductive performances of male rats.

Mercury disrupts redox status, up-regulates metallothionein and induces genotoxicity in respiratory tree of sea cucumber (Holothuria forskali).

Mercury (Hg) is among the most deleterious contaminant in the aquatic environment and presents a serious risk to humans and ecosystems. This study evaluated the effects of Hg on oxidative stress biomarkers, DNA integrity and histological structure of the respiratory tree of Holothuria forskali exposed to different concentrations of mercury chloride HgCl2 (0.04, 0.08 and 0.16 mg L-1) for 96 h. Exposure of H. forskali to Hg led to oxidative stress with an increase in Malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein product (AOPP) and protein carbonyls (PCO) levels in the treated groups. Alteration of the antioxidant system was also confirmed by the significant increase in glutathione (GSH), nonprotein thiol (NPSH) and vitamin C contents. Moreover, the enzymatic activity of superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Catalase (CAT) increased significantly. Our research revealed that total Metallothionein (MTs) content enhanced in a dose-dependent manner. Interestingly, the exposure to this metal provoked a decrease in Acetylcholinesterase (AChE) activity. Hg genotoxicity was further evidenced by a random DNA degradation that was observed in the treated groups. The histopathological findings confirmed the biochemical results. Overall, our results indicated that mercury-induced genotoxicity, oxidative damage and histopathological injuries in the respiratory tree of H. forskali.