Effects Of Tributyltin Exposure Research Articles

Embryonic exposure to environmentally relevant levels of tributyltin affects embryonic tributyltin bioaccumulation and the physiological responses of juveniles in cuttlefish (Sepia pharaonis)

Tributyltin (TBT) is a typical organic pollutant that persists in aquatic sediments due to its wide usage as an antifouling fungicide during the past few decades. Despite increased awareness of the serious negative consequences of TBT on aquatic species, studies on the effects of TBT exposure on cephalopod embryonic development and juvenile physiological performance are scarce. To investigate the lasting effects of TBT toxicity on Sepia pharaonis from embryo to hatchling, embryos (gastrula stage, 3–5 h post fertilization) were exposed to four levels of TBT until hatching: 0 (control), 30 (environmental level), 60, and 120 ng/L. Subsequently, juvenile growth performance endpoints and behavioral alterations were assessed over 15 days post-hatching. Egg hatchability was significantly reduced and embryonic development (i.e., premature hatching) was accelerated in response to 30 ng/L TBT exposure. Meanwhile, TBT-induced alterations in embryonic morphology primarily included yolk-sac lysis, embryonic malformations, and uneven pigment distributions. During the pre-middle stage of embryonic development, the eggshell serves as an effective barrier to safeguard the embryo from exposure to 30–60 ng/L TBT, according to patterns of TBT accumulation and distribution in the egg compartment. However, even environmental relevant levels of TBT (30 ng/L) exposure during embryonic development had a negative impact on juvenile behavior and growth, including slowing growth, shortening eating times, causing more irregular movements, and increasing inking times. These findings indicate that after TBT exposure, negative long-lasting effects on S. pharaonis development from embryo to hatchling persist, suggesting that long-lasting toxic effects endure from S. pharaonis embryos to hatchlings.

Mapping of lymphocyte densities in postmortem brains of schizophrenic and depressed patients. Evidence of neuroinflammation in subgroups of patients

RNA-sequencing was used to identify sex-biased gene expression in brains of rare minnow (Gobiocypris rarus) by comparing transcriptomic profiles between females and males. Furthermore, transcriptomic responses to 10 ng/L tributyltin (TBT) in both male and female brains were also investigated to understand whether TBT affects the identified sex-biased genes. Differentially expressed genes (DEGs) were identified using the IDEG6 web tool. In this article, we presented male- and female-biased DEGs, and up-regulated and down-regulated DEGs after TBT exposure. The raw reads data supporting the present analyses has been deposited in NCBI Sequence Read Archive (SRA, http://www.ncbi.nlm.nih.gov/Traces/sra) with accession number PRJNA376634. The data presented in this article are related to the research article entitled “Transcriptomic analyses of sexual dimorphism of rare minnow (G. rarus) brains and effects of tributyltin exposure” (doi: 10.1016/j.ecoenv.2018.02.049).

Differential gene expression in the brain of Cuvier, Sebastiscus marmoratus, in response to exposure to tributyltin

Tributyltin (TBT), a ubiquitous marine environmental contaminant, has been reported to affect functioning of the central nervous system. However, the mechanism of its neurotoxicity remains unknown. The effects of TBT exposure on the Sebastiscus marmoratus were investigated using a suppression subtractive hybridisation (SSH) combined with mirror orientation selection (MOS) method. A total of 50 candidate clones from SSH libraries were picked for sequencing and homology searching. The results showed that 23 unique differentially expressed genes were obtained, including 11 up-regulated and 12 down-regulated fragments. The functions with which they are associated include energy-related metabolism, polypeptide translation and location, mitosis and cell proliferation. Expression of 11 candidate genes was analysed in brain by real-time fluorescent quantitative PCR. The present study provided a basis for investigating the response of fish to TBT exposure and allowed the characterisation of new potential neurotoxic biomarkers of TBT contamination in seawater.

Abstract 3191: Elevation of tumor-promoting cytokines in mice exposed to the environmental contaminant tributyltin

Abstract Cytokines are important regulators of immune responsiveness. Alterations of cytokine secretion from immune cells would have the potential to disrupt both immune destruction of cancer cells and to alter the proliferation and invasiveness of tumor cells due to their capacity to act as growth factors, angiogenic factors, and inducers of epithelial-mesenchymal transition. Tributyltin (TBT) is a widespread environmental contaminant having been used in a variety of industrial applications and is found in human blood at levels ranging as high as 261 nM. Studies in human immune cells have shown that secretion of tumor necrosis factor alpha (TNFα) is altered by exposures to TBT. There have been no in vivo studies of the effects of exposure to TBT on the cytokine communication network. As it is not possible to examine alterations of this network in exposed humans, we examined the effects of TBT exposure in a mouse model using Milliplex mouse cytokine/chemokine magnetic bead premixed 32 plex kit. Serum and spleens of TBT-exposed mice were analyzed for changes in cytokine secretion/levels. TBT increased the levels of IL13 in the serum of non-tumor-bearing mice and increased IL1β, IL6, KC, and M-CSF in tumor-bearing mice. The spleens of both non-tumor-bearing and tumor-bearing mice showed increases in Eotaxin when exposed to TBT. Of significant interest is the fact that the presence of tumor causes increases in Eotaxin, IL12p40, M-CSF, and TNFα and exposure to TBT alone can cause increases in these same cytokines. Tumors are known to increase levels of cytokines that enhance their ability to survive. The results showing that TBT can amplify the levels of several cytokines that are increased by tumor suggest that TBT may have tumor-promoting abilities by modulating tumor growth and/or invasiveness. Experiments are under way to dissect cytokine signaling pathways that are affected by TBT. The findings will allow identification of molecular targets that are necessary to intercept the tumor promoting signaling following TBT exposure. Supported by: NIH grant 5U54CA163066-03 Citation Format: Shanieek Lawrence, Samuel Troy Pellom, Tasia Hurd-Brown, Anil Shanker, Margaret Whalen. Elevation of tumor-promoting cytokines in mice exposed to the environmental contaminant tributyltin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3191. doi:10.1158/1538-7445.AM2014-3191

Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases.

Effects of tributyltin exposure in hermit crabs: Clibanarius vittatus as a model

Tributyltin (TBT) contamination affects the reproductive system of many species of invertebrates worldwide. The present study was designed to evaluate the effects of exposure to TBT pollution on the reproduction of the hermit crab Clibanarius vittatus. An orthogonal experiment was designed with two treatments: contamination (with or without TBT in the food) and crab sex (males and females). The animals were reared in the laboratory for nine months, and macroscopic and histological analyses of reproductive organs were carried out after the end of the experiment. Tributyltin was recorded in exposed crabs, but no morphological alterations were detected in the gonads of males, regardless of whether they were exposed to TBT. In contrast, females exposed to TBT displayed disorganization and atrophy of their ovaries, thus directly affecting reproduction in this hermit crab species. This effect observed in female hermit crabs may harm populations located in harbor regions, where TBT concentration is high, even after the worldwide TBT ban.

Immune-Regulatory Transcriptional Responses in Multiple Organs of Atlantic Salmon After Tributyltin Exposure, Alone or in Combination with Forskolin

Tributyltin (TBT) is a widespread marine pollutant that influences physiological conditions of fish and other aquatic organisms. In addition to effects on reproduction, the immune system has been proposed as a possible target for TBT effects. In the present study, the effects of TBT exposure were examined on the expression of genes involved in immune system compentence in liver and head kidney of Atlantic salmon, in the presence and absence of a second-messenger activator (forskolin). Juvenile salmon were force-fed a diet containing TBT (0—solvent control, 0.1, 1, or 10 mg/kg fish) for 72 h. Consequently, fish from the control group and 10-mg/kg TBT group were exposed to the adenylate cyclase (AC) activator forskolin (200 μg/L) for 2 or 4 h. Forskolin was selected for this study because it is known to exhibit potent immune system enhancement by activating macrophages and lymphocytes. After sacrifice, liver and head kidney were sampled and transcript changes for interleukin (IL)-1β, IL-10, transforming growth factor (TGF) β, interferon (INF) α, INFγ, tumor necrosis factor (TNF) α, Mx3, and insulin-like growth factor (IGF)-1 were determined in both tissues by quantitative polymerase chain reaction (qPCR) using gene-specific primers. TBT, when given alone and also in combination with forskolin, decreased IL-1β, TNFα, IFNγ, IFNα, Mx3, and IGF-1 gene expression. In contrast, IL-10 and TGFβ transcripts were increased after TBT exposure alone and also in combination with forskolin. Generally, these effects were largely dependent on TBT dose and time of exposure when given in combination with forskolin. Overall, our findings suggest a possible immunomodulatory effect of TBT, possibly involving cAMP activation.

Persistent immunotoxic effects of tributyltin in human natural killer cells can be reversed by interleukin 2

Tributyltin (TBT) is a widespread environmental contaminant due to its use in marine antifouling paints and as an anti-microbial agent in other applications. There are measurable levels of TBT in some samples of human blood. Natural killer (NK) cells are lymphocytes capable of killing tumor and virally infected cells. Previously, we have shown that a 1 h exposure to 300 nM TBT caused a permanent decrease in the ability of human NK cells to bind to and destroy tumor target cells and in their expression of certain functionally relevant cell surface markers. The present study investigates the effect of the NK-stimulatory cytokine, interleukin (IL) 2 on TBT-induced decreases in NK cytotoxicity, binding function, and expression of CD16 and CD56. A 1 h exposure to 300 nM TBT followed by 24 h in TBT-free media decreased cytotoxic function by 80%, and expression of CD16 by 16%. When 10 ng/mL IL-2 was present during the 24 h incubation there was no statistically significant decrease in cytotoxicity or expression of CD16. A 96 h incubation in TBT-free media produced decreases in cytotoxicity (99%), binding function (65%), and expression of CD16 (48%) and CD56 (51%). IL-2 was able to reverse the TBT-induced decreases in each of these parameters seen after 96 h. These results suggest that IL-2 restoration of NK ability to bind target cells correlates with its ability to restore CD16 and CD56 expression. Additionally, neither the loss of cytotoxic function (seen in the 24 or 48 h periods following TBT exposure) nor its restoration by IL-2 can be substantially explained by the effects of TBT exposure on CD16 and CD56 expression or target binding.

Effects of tributyltin on the survival in the caprellid amphipod Caprella danilevskii

The caprellid amphipod Caprella danilevskii was exposed to five levels (0, 10, 100, 1000 and 10 000 ng l−1) of tributyltin (TBT) both in the embryonic stage (5 days) and over its whole life history from hatch to death (50 days) to examine the effects of TBT exposure on survival. In both experiments, survival rate decreased drastically as TBT concentrations increased, with a decrease occurring even at 10 ng l−1 in both short- and long-term exposure experiments. Significant differences were found in the survival rate between the control (no control specimens died) and the three concentration groups except 10 000 ng l−1 (all specimens died), regardless of sex. However, the survival rate in response to exposure to TBT has been found to be similar among all combinations of TBT concentration except 10 000 ng l−1, in both sexes. Furthermore, no significant differences were observed in the survival rate in response to exposure to each concentration of TBTCl between sexes. These findings suggest that the risk of survival in response to exposure to TBT between sexes is similar in the caprellids. No sex-specific differences of mortality by TBT exposure were observed in the species although feminization by TBT exposure was found in the caprellids in a previous study. These results all lead to the conclusion that TBT disturbs the mechanism of sex determination during the embryonic stage of the species.

Effects of tributyltin exposure in the embryonic stage on sex ratio and survival rate in the caprellid amphipod Caprella danilevskii

In order to examine the biological effects of tributyltin (TBT) exposure, the caprellid amphipod Caprella danilevskii was exposed to 5 levels (0, 10, 100, 1000 and 10 000 ng l -1 ) of TBT dur- ing the embryonic stage (5 d). The male and female ratios changed dramatically in the hatched juve- nile with increases in TBT concentrations; i.e. the proportion of females was found to increase to 55.6% at 10 ng l -1 , 85.7% at 100 ng l -1 and 81.8% at 1000 ng l -1 . All specimens died in 10 000 ng TBTCl l -1 within 5 d after spawning due to the acute toxic concentration for the species. No signifi- cant differences were observed to occur in the sex ratio in response to the exposure after hatching (50 d) in a previous study. Sex disturbance might therefore be induced during the embryonic stage in the caprellid. Reproductive inhibitions such as brood loss and oogenesis inhibition occurred even at 10 to 100 ng TBTCl l -1 exposures in the short term in both parental females and their offspring females. The survival rate decreased drastically as the TBT concentrations increased, with the decrease being observed at TBT concentrations as low as 10 ng l -1 (69%) in the offspring. In parental females, the survival rate also decreased at more than 100 ng TBTCl l -1 , despite movement after 5 d into the no-TBT-added seawater. Therefore, our data suggest that nanogram concentrations of TBT similar to those encountered in coastal waters can directly affect sex ratio, reproduction and survival in the caprellid, and this phenomenon occurs at environmentally realistic concentrations in the coastal ecosystem.