Tributyltin Research Articles

Effects of Exposure to Trade Antifouling Paints and Biocides on Larval Settlement and Metamorphosis of the Compound Ascidian Botryllus schlosseri

To evaluate the effects of antifouling paints and biocides on larval settlement and metamorphosis, newly hatched swimming larvae of the compound ascidian Botryllus schlosseri, a dominant species of soft-fouling in coastal communities, were exposed to (i) substrata coated with seven antifouling paints on the market containing different biocidal mixtures and types of matrices and (ii) sea water containing various concentrations of eight biocidal constituents. All antifouling paints showed high performance, causing 100% mortality and metamorphic inhibition, with ≥75% not-settled dead larvae. All antifouling biocides prevented the settlement of larvae. The most severe larval malformations, i.e., (i) the formation of a bubble encasing the cephalenteron and (ii) the inhibition of tail resorption, were observed after exposure to metal and organometal compounds, including tributyltin (TBT) at 1 μM (325.5 µg L−1), zinc pyrithione (ZnP) at 1 μM (317.7 µg L−1), and CuCl at 0.1 μM (98.99 µg L−1), and to antimicrobials and fungicides, including Sea-Nine 211 at 1 μM (282.2 µg L−1) and Chlorothalonil at 1 μM (265.9 µg L−1). The herbicides seemed to be less active. Irgarol 1051 was not lethal at any of the concentrations tested. Diuron at 250 μM (58.2 mg L−1) and 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine (TCMS pyridine) at 50 μM (14.8 mg L−1) completely inhibited larval metamorphosis. These results may have important implications for the practical use of different antifouling components, highlighting the importance of their testing for negative impacts on native benthic species.

Removal of organotin compounds and metals from Swedish marine sediment using Fenton\u2019s reagent and electrochemical treatment

Metal and tributyltin (TBT) contaminated sediments are problematic for sediment managers and the environment. This study is the first to compare Fenton’s reagent and electrochemical treatment as remediation methods for the removal of TBT and metals using laboratory-scale experiments on contaminated dredged sediment. The costs and the applicability of the developed methods were also compared and discussed. Both methods removed > 98% TBT from TBT-spiked sediment samples, while Fenton’s reagent removed 64% of the TBT and electrolysis 58% of the TBT from non-spiked samples. TBT in water phase was effectively degraded in both experiments on spiked water and in leachates during the treatment of the sediment. Positive correlations were observed between TBT removal and the added amount of hydrogen peroxide and current density. Both methods removed metals from the sediment, but Fenton’s reagent was identified as the most potent option for effective removal of both metals and TBT, especially from highly metal-contaminated sediment. However, due to risks associated with the required chemicals and low pH level in the sediment residue following the Fenton treatment, electrochemical treatment could be a more sustainable option for treating larger quantities of contaminated sediment.

Tributyltin inhibits autophagy by decreasing lysosomal acidity in SH-SY5Y cells

Tributyltin (TBT) is an environmental pollutant that remains in marine sediments and is toxic to mammals. For example, TBT elicits neurotoxic and immunosuppressive effects on rats. However, it is not entirely understood how TBT causes toxicity. Autophagy plays a pivotal role in protein quality control and eliminates aggregated proteins and damaged organelles. We previously reported that TBT dephosphorylates mammalian target of rapamycin (mTOR), which may be involved in enhancement of autophagosome synthesis, in primary cultures of cortical neurons. Autophagosomes can accumulate due to enhancement of autophagosome synthesis or inhibition of autophagic degradation, and we did not clarify whether TBT alters autophagic flux. Here, we investigated the mechanism by which TBT causes accumulation of autophagosomes in SH-SY5Y cells. TBT inhibited autophagy without affecting autophagosome–lysosome fusion before it caused cell death. TBT dramatically decreased the acidity of lysosomes without affecting lysosomal membrane integrity. TBT decreased the mature protein level of cathepsin B, and this may be related to the decrease in lysosomal acidity. These results suggest that TBT inhibits autophagic degradation by decreasing lysosomal acidity. Autophagy impairment may be involved in the mechanism underlying neuronal death and/or T-cell-dependent thymus atrophy induced by TBT.

The Preservation of PPARγ Genome Duplicates in Some Teleost Lineages: Insights into Lipid Metabolism and Xenobiotic Exploitation.

Three peroxisome proliferator-activated receptor paralogues (PPARα, -β and -γ) are currently recognized in vertebrate genomes. PPARγ is known to modulate nutrition, adipogenesis and immunity in vertebrates. Natural ligands of PPARγ have been proposed; however, the receptor also binds synthetic ligands such as endocrine disruptors. Two paralogues of PPARα and PPARβ have been documented in teleost species, a consequence of the 3R WGD. Recently, two PPARγ paralogue genes were also identified in Astyanax mexicanus. We aimed to determine whether the presence of two PPARγ paralogues is prevalent in other teleost genomes, through genomic and phylogenetic analysis. Our results showed that besides Characiformes, two PPARγ paralogous genes were also identified in other teleost taxa, coinciding with the teleost-specific, whole-genome duplication and with the retention of both genes prior to the separation of the Clupeocephala. To functionally characterize these genes, we used the European sardine (Sardina pilchardus) as a model. PPARγA and PPARγB display a different tissue distribution, despite the similarity of their functional profiles: they are unresponsive to tested fatty acids and other human PPARγ ligands yet yield a transcriptional response in the presence of tributyltin (TBT). This observation puts forward the relevance of comparative analysis to decipher alternative binding architectures and broadens the disruptive potential of man-made chemicals for aquatic species.

Geochemical tests to study the effects of cement ratio on potassium and TBT leaching and the pH of the marine sediments from the Kattegat Strait, Port of Gothenburg, Sweden

Cement is a key construction material in civil and geotechnical engineering. However, its application for stabilization of marine sediments needs further investigation. This paper tests the effects of varied amounts of Portland cement added to soil samples on the leaching of tributyltin (TBT) from the contaminated marine sediments and evaluates the pH level. Identifying the best combinations of Portland cement / slag / Cement Kiln Dust (CKD) for effective treatment of soil samples is a central challenge in marine geotechnical investigations with major implications for stabilization of dragged coastal sediments. The paper aims to test the TBT leaching as well as pH level and potassium (K) content in soil samples. Materials included marine sediments collected from the seabed of the Port of Gothenburg, Kattegat Strait, southwest Sweden. The methodology applied the existing specifications of the Swedish Institute for Standards (SIS) for geochemical tests of soil stabilized by Portland cement/slag/CKD. Leaching in soil samples was examined for 2.25, 9 and 36 days. Variations in the speed of decline of TBT leaching were noted depending on the ratio of Portland cement. The methodology follows the SIS instructions regarding the procedure of leaching tests: SS-EN 15863. Mixtures with pure Portland cement and cement / CKD gave pH values between 11.5–12 in the surface leaching experiments. Mixing of slag / CKD or slag lowered the pH range to 11–11.5 and 10–10.5, respectively. The leaching of TBT was affected by the changed amounts of seawater in the surface leaching experiments. The study shows that leaching reduces over time when the mobile fraction is being washed away and replaced by other leaching mechanisms and processes. Furthermore, in models in which leaching of TBT and potassium were assessed, there were, on average, changes in behaviour on the 9th day during the experiment time treatment and stabilization afterwards.

Resveratrol ameliorates polycystic ovary syndrome via transzonal projections within oocyte-granulosa cell communication.

Rationale: Polycystic ovary syndrome (PCOS) is closely linked to follicular dysplasia and impaired bidirectional oocyte-granulosa cell (GC) communication. Given that PCOS is a heterogeneous, multifactorial endocrine disorder, it is important to clarify the pathophysiology of this ovarian disease and identify a specific treatment.Methods: We generated PCOS rat models based on neonatal tributyltin (TBT) exposure and studied the therapeutic effect and mechanism of resveratrol (RSV), a natural plant polyphenol. Transcriptome analysis was conducted to screen the significantly changed pathways, and a series of experiments, such as quantitative real-time polymerase chain reaction (PCR), Western blot and phalloidin staining, were performed in rat ovaries. We also observed similar changes in human PCOS samples using Gene Expression Omnibus (GEO) database analysis and quantitative real-time PCR.Results: We first found that injury to transzonal projections (TZPs), which are specialized filopodia that mediate oocyte-GC communication in follicles, may play an important role in the etiology of PCOS. We successfully established PCOS rat models using TBT and found that overexpressed calcium-/calmodulin-dependent protein kinase II beta (CaMKIIβ) inhibited TZP assembly. In addition, TZP disruption and CAMK2B upregulation were also observed in samples from PCOS patients. Moreover, we demonstrated that RSV potently ameliorated ovarian failure and estrus cycle disorder through TZP recovery via increased cytoplasmic calcium levels and excessive phosphorylation of CaMKIIβ.Conclusions: Our data indicated that upregulation of CaMKIIβ may play a critical role in regulating TZP assembly and may be involved in the pathogenesis of PCOS associated with ovarian dysfunction. Investigation of TZPs and RSV as potent CaMKIIβ activators provides new insight and a therapeutic target for PCOS, which is helpful for improving female reproduction.

Solid-state 1H NMR-based metabolomics assessment of tributylin effects in zebrafish bone

Tributyltin (TBT), an endocrine disruptor is used globally in agribusiness and industries as biocides, heat stabilizers, and in chemical catalysis. It is known for its deleterious effects on bone by negatively impacting the functions of osteoblasts, osteoclasts and mesenchymal stem cells. However, the impact of TBT on the metabolomics profile in bone is not yet studied. Here, we demonstrate alterations in chemical metabolomics profiles measured by solid state 1H nuclear magnetic resonance (1H NMR) spectroscopy in zebrafish bone following tributyltin (TBT) treatment. TBT of 0, 100, 200, 300, 400 and 500 μg/L were exposed to zebrafish. From this, zebrafish bone has subjected for further metabolomics profiling. Samples were measured via one-dimensional (1D) solvent -suppressed and T2- filtered methods with in vivo zebrafish metabolites. A dose dependent alteration in the metabolomics profile was observed and results indicated a disturbed aminoacid metabolism, TCA cycle, and glycolysis. We found a significant alteration in the levels of glutamate, glutamine, glutathione, trimethylamine N-oxide (TMAO), and other metabolites. This investigation hints us the deleterious effects of TBT on zebrafish bone enabling a comprehensive understanding of metabolomics profile and is expected to play a crucial role in understanding the deleterious effects of various endocrine disruptor on bone.

Imposex incidence in the sandy beach snail Hastula cinerea reveals continued and widespread tributyltin contamination after its international ban

Tributyltin (TBT) contamination is a prominent issue in coastal areas. However, TBT contamination in sandy beaches, which dominate the seascape of some regions, is not well understood. Imposex monitoring in beach gastropods may help widen the spatial coverage of surveillance efforts to enforce TBT ban regulations. In this study, we assessed imposex occurrence in the beach snail Hastula cinerea from August 2019 to February 2020 in southeastern Brazil. Imposex was observed in 14 of the 23 sampled beaches, and the highest imposex levels were recorded at beaches with nautical activities, including a beach located in a no-take protected insular area. Imposex was absent in the beaches that were consistently exposed to wave energy and less subjected to boating activities. The imposex incidence in H. cinerea after 11 years of the TBT international ban suggests persistent and widespread TBT contamination in the studied beaches, a phenomenon that should be widely assessed.

Tributyltin and the Female Hypothalamic-Pituitary-Gonadal Disruption.

The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng-20 ng/ml) and in vivo (10 ng-20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction.

Evaluation of Different Binder Combinations of Cement, Slag and CKD for S/S Treatment of TBT Contaminated Sediments

Abstract The seabed in the ports needs to be regularly cleaned from the marine sediments for safe navigation. Sediments contaminated by tributyltin (TBT) are environmentally harmful and require treatment before recycling. Treatment methods include leaching, stabilisation and solidification to remove toxic chemicals from the sediments and improve their strength for reuse in the construction works. This study evaluated the effects of adding three different binder components (cement, cement kiln dust (CKD) and slag) to treat sediment samples collected in the port of Gothenburg. The goal of this study is to assess the leaching of TBT from the dredged marine sediments contaminated by TBT. The various methods employed for the treatment of sediments include the application of varied ratios of binders. The project has been performed by the Swedish Geotechnical Institute (SGI) on behalf of the Cementa (HeidelbergCement Group) and Cowi Consulting Group, within the framework of the Arendal project. An experiment has been designed to evaluate the effects of adding CKD while reducing cement and slag for sediment treatment. Methods that have been adopted include laboratory processing of samples for leaching using different binder combinations, followed by statistical data processing and graphical plotting. The results of the experiment on leaching of TBT for all samples are tested with a varied ratio of cement, slag, CKD and water. Specimens with added binders ‘cement/CKD’ have demonstrated higher leaching compared to the ratio ‘cement/slag/CKD’ and ‘cement/slag’. The ‘CKD/slag’ ratio has presented the best results followed by the ‘cement/slag/CKD’, and can be used as an effective method of s/s treatment of the sediments. The results have shown that the replacement of cement and slag by CKD is effective at TBT leaching for the treatment of toxic marine sediments contaminated by TBT.

Field Notes on Sex-Bias in Gibberulus dekkersi Maxwell, Hernandez Duran, Rowell & Rymer, 2021 (Gastropoda: Neostromboidae: Strombidae) on the Great Barrier Reef

The investigation of sex bias and pseudohermaphroditism is a relatively unexplored area of research in the Neostromboidae. Here, we inform on these phenomena in a population of Gibberulus dekkersi Maxwell, Hernandez Duran, Rowell & Rymer, 2021 on Green Island, Great Barrier Reef. We collected 598 individuals, and noted the size of the cluster in which it occurred. Each individual was placed ventral side up and the body of the animal observed at the time of righting. Sex was determined by the presence or absence of a verge. During this sexing process, females were inspected for the presence of external male sexual organs to indicate the presence or absence of pseudohermaphroditism. We found that, overall, the population was not sexually biased towards one sex. However, we did find that individual clusters within the population showed significant sex bias, with different clusters favouring either males or females. Smaller clusters had a structural sex-ratio bias in favour of females. No evidence for pseudohermaphroditism was recorded, which indicates that the marine pollutant tributyltin (TBT) may not be present or at harmful levels in the surrounding environment. This study adds information from an unstudied Queensland taxon to the growing evidence on sex bias, clustering effects and pseudohermaphroditism within the Neostromboidae.

Oral Exposure to Tributyltin Induced Behavioral Abnormality and Oxidative Stress in the Eyes and Brains of Juvenile Japanese Medaka (Oryzias latipes).

The widely used compound tributyltin (TBT), which can be continuously detected in aquatic species and seafood, may induce diverse adverse effects on aquatic organisms. However, little is known regarding the mechanistic links between behavioral abnormality and oxidative stress in different fish tissues in response to oral TBT exposure. Herein, juvenile Japanese medaka (Oryzias latipes) were orally exposed to TBT at 1 and 10 ng/g-bw/d for four weeks. After exposure, the locomotor activity and social interaction of juvenile medaka were found to be significantly reduced in the 10 ng/g-bw/d TBT-exposed group. Furthermore, the antioxidant biomarkers in different tissues of juvenile medaka showed different levels of sensitivity to TBT exposure. The eye superoxide dismutase (SOD) activities markedly increased in both groups exposed to 1 and 10 ng/g-bw/d TBT, while the eye and brain malondialdehyde (MDA) levels increased in the higher dose group. Furthermore, the eye and brain ATPase activities markedly declined in the 1 ng/g-bw/d TBT-exposed group. A correlation analysis revealed that the decreased locomotor activity and social interaction in medaka were associated with the eye antioxidant enzyme (i.e., SOD and catalase (CAT)) activity and brain oxidative damage level. Thus, our findings suggested that there might be some mechanistic links between the behavioral abnormality induced by TBT exposure and oxidative stress in the eyes and brains of medaka. Thus, our findings indicate that the impacts of oral exposure to TBT should be considered to better assess its risk to the aquatic ecosystem and human health.

Effects of tributyltin on retinoid X receptor gene expression and global DNA methylation during intracapsular development of the gastropod Tritia mutabilis (Linnaeus, 1758)

The tributyltin (TBT)-mediated induction of imposex in marine snails is considered a common mechanism of endocrine disruption through the retinoid X receptor (RXR)-dependent pathway. However, there is evidence that regulation of RXR also relates to metabolic processes, differentiation, apoptosis, and embryonic development, playing a key role in molluscan neuronal differentiation and organogenesis. In this regard, very little is known about the gastropod Tritia mutabilis especially in relation to the effects of TBT exposure during intracapsular embryonic development. In this study, we have investigated the RXR expression fold changes of T. mutabilis encapsulated embryos exposed to different concentrations (10−10 to 10−12 M) of TBT up to 10 days of treatment. We demonstrate that RXR is sequentially expressed during development and that exposure to the lowest and highest TBT doses induces time-dependent changes in RXR gene transcription. We also show that TBT treatment is associated with global DNA demethylation and reduced DNA-methyltransferase I (DNMT1) expression and activity levels. Overall, our data indicate that RXR has important functions during the early stages of T. mutabilis embryo development and is involved in mediating the potential epigenetic alterations induced by TBT exposure.

Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice

Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We previously reported that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in vivo. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with vehicle or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed either diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat. These results show that TBT protects against trabecular bone loss, even in the presence of a strongly resorptive environment, at an even lower level of exposure than we showed repressed homeostatic resorption.

An absurd scenario in 2021: Banned TBT-based antifouling products still available on the market

Despite the efforts of the International Marine Organization (IMO), through the International Convention on the Control of Harmful Antifouling Systems on Ships to ban the use of TBT-based antifouling paints (September 2008), and the Rotterdam Convention (RC) to forbid the trade of tributyltin (TBT), the situation does not seem to have significantly changed since 2014 when TBT-based paints were shown to be still being manufactured in the United States and offered for sale in stores throughout the Caribbean and Central America. In fact, this study shows that seven years later the same situation not only persists, but may have an even more global distribution than previously thought.

Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT.

Background:Endocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.Objectives:We sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.Methods:We used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.Results:Metabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.Discussion:This study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.

Effects of chronic exposure to environmental levels of tributyltin on the lined seahorse (Hippocampus erectus) liver: Analysis of bioaccumulation, antioxidant defense, and immune gene expression

Tributyltin (TBT), an organotin compound frequently detected in the coastal environments, poses a threat to aquatic organisms. The lined seahorse (Hippocampus erectus) is a vulnerable species found in nearshore water habitats. The mechanisms by which this fish responds to TBT exposure are not yet fully understood. Histological, biochemical, and transcriptional analyses were conducted, and the results showed that 60 days of exposure to 50 and 500 ng/L TBT caused significant tin accumulation and liver damage to seahorses. Antioxidant defenses and immune responses to TBT exposure in the livers of seahorses were further investigated. The enzymatic activity of superoxide dismutase and malondialdehyde content increased, while catalase activity decreased. Transcriptomic analysis revealed that a series of genes involved in the antioxidant defense system were highly induced to protect the hepatic cells from oxidative damage. TBT exposure also resulted in the induction of genes associated with immune and inflammatory processes, representing a stress response to combat the adverse environmental conditions in the exposed seahorses. Furthermore, seahorses showed an increased health risk, according to the elevation of the expression of genes with tumor-promoting effects, when exposed to TBT. These findings contribute to our understanding of the adverse effects of TBT exposure on seahorses, and their potential defense mechanisms.

Changes in the colour and photosynthetic efficiency of the hermatypic coral Acropora tenuis exposed to Irgarol 1051 at 30 °C seawater temperature

Besides global warming, coral reefs face various anthropogenic threats, including watershed-based and marine-based contaminants. Recently, Irgarol 1051, a photosystem II herbicide, has been introduced as a “booster” agent in copper-based antifouling paints after global ban of tributyltin (TBT) in January 2008. Irgarol is considered to pose a potential risk to corals. In this study, a clone of Acropora tenuis separated from the colony collected from Sesoko Island, Okinawa, southern Japan, was exposed to 1.0 μg L−1 Irgarol at 27.5 °C and 30.0 °C (higher than the temperature in the warmest month in southern Japan) for 7 d. The coral colour was converted to RGB values, ranging from 0 (darkest) to 255 (brightest). The RGB values under both temperature treatments slightly decreased in the control (no herbicide exposure), but those in both 27.5 °C and 30.0 °C Irgarol treatments increased after day 3. The maximum effective quantum yield (ΔF/Fm′) slightly increased in both 27.5 °C and 30.0 °C control treatments, but decreased in 27.5 °C and 30.0 °C Irgarol treatments after day 1. The exposure to 1.0 μg L−1 Irgarol induced significant differences in RGB values and ΔF/Fm′ compared with those in the control at the same temperature. Regarding the temperature difference (27.5 °C vs. 30.0 °C), no significant differences in RGB values and ΔF/Fm′ were detected in both control and Irgarol treatments. Our results revealed no significant combined effect of Irgarol exposure and 30.0 °C on A. tenuis. These findings suggest that 30.0 °C is a normally inhabitable environmental temperature for A. tenuis. The bleaching of A. tenuis is more likely caused by the exposure to 1.0 μg L−1 Irgarol than by the exposure to high seawater temperature of 30.0 °C.

An ancestral nuclear receptor couple, PPAR-RXR, is exploited by organotins

Environmental chemicals have been reported to greatly disturb the endocrine and metabolic systems of multiple animal species. A recent example involves the exploitation of the nuclear receptor (NR) heterodimeric pair composed by PPAR/RXR (peroxisome proliferator-activated receptor/retinoid X receptor), which shows lipid perturbation in mammalian species. While gene orthologues of both of these receptors have been described outside vertebrates, no functional characterization of PPAR has been carried in protostome lineages. We provide the first functional analysis of PPAR in Patella sp. (Mollusca), using model obesogens such as tributyltin (TBT), triphenyltin (TPT), and proposed natural ligands (fatty acid molecules). To gain further insights, we used site-directed mutagenesis to PPAR and replaced the tyrosine 277 by a cysteine (the human homologous amino acid and TBT anchor residue) and an alanine. Additionally, we explored the alterations in the fatty acid profiles after an exposure to the model obesogen TBT, in vivo. Our results show that TBT and TPT behave as an antagonist of Patella sp. PPAR/RXR and that the tyrosine 277 is important, but not essential in the response to TBT. Overall, these results suggest a relation between the response of the mollusc PPAR-RXR to TBT and the lipid profile alterations reported at environmentally relevant concentrations. Our findings highlight the importance of comparative analysis between protostome and deuterostome lineages to decipher the differential impact of environmental chemicals.

Integration of data from the cell-based ERK1/2 ELISA and the Comparative Toxicogenomics Database deciphers the potential mode of action of bisphenol A and benzo[a]pyrene in lung neoplasm

Chemicals can activate a variety of signaling pathways, initiating changes in gene expression and cellular functions. Here, we combined experimental data on the chemical-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation with the Comparative Toxicogenomics Database (CTD) to connect signaling, genes, and phenotypes to reveal the potential chemical's mode of action (MOA) responsible for the disease state. Experimental data on ERK1/2 activation were derived from the cell-based phospho-ERK1/2 ELISA on human alveolar epithelial cells A549. A549 cells were exposed to bisphenol A (BPA), benzo[a]pyrene (BaP), tributyltin (TBT), and ibuprofen from 10−12 M to 10−5 M. Results show that BPA, BaP, and TBT can activate ERK1/2 in A549 cells. We selected BPA and BaP to elucidate the molecular events connecting chemical exposure, ERK1/2 signaling, phenotypes, and lung neoplasm (LN) using CTD. CTD analysis showed that BPA and BaP share 26 mitogen-activated protein kinase 1/3 (MAPK1/3) signaling genes associated with LN. Phenotype prioritization revealed 37 BPA, 10 BaP, and 11 shared key phenotypes associated with LN. Alignment of MAPK1/3 signaling genes and phenotypes showed that ERK1/2 and oxidative stress, EGFR gene, and positive regulation of cell proliferation and migration could be the shared key events (KE) for BPA and BaP. This analysis also identified protein kinase B and ERK1/2 signaling, FGF9, FGFR1 and FGFR2 genes, positive regulation of cell proliferation and angiogenesis as KE in MOA for BPA, whereas ERK1/2 signaling, IL6 and DAB2IP genes, negative regulation of cell proliferation and inflammatory response were identified as KE in MOA for BaP.