Environmental Obesogens: Mechanisms and Controversies.

Obesity is a worldwide pandemic in adults as well as children and adds greatly to health care costs through its association with type 2 diabetes, metabolic syndrome, cardiovascular disease, and cancers. The prevailing medical view of obesity is that it results from a simple imbalance between caloric intake and energy expenditure. However, numerous other factors are important in the etiology of obesity. The obesogen hypothesis proposes that environmental chemicals termed obesogens promote obesity by acting to increase adipocyte commitment, differentiation, and size by altering metabolic set points or altering the hormonal regulation of appetite and satiety. Many obesogens are endocrine disrupting chemicals that interfere with normal endocrine regulation. Endocrine disrupting obesogens are abundant in our environment, used in everyday products from food packaging to fungicides. In this review, we explore the evidence supporting the obesogen hypothesis, as well as the gaps in our knowledge that are currently preventing a complete understanding of the extent to which obesogens contribute to the obesity pandemic.

Elemental-Sulfur-Enabled Divergent Synthesis of Disulfides, Diselenides, and Polythiophenes from ß-CF3 -1,3-Enynes.

Divergent synthesis for precise constructions of cyclic unsymmetrical diaryl disulfides or diselenides and polythiophenes from CF3 -containing 1,3-enynes and S8 was developed when the ortho group is F, Cl, Br, and NO2 on aromatic rings. Meanwhile, disulfides (diselenides) were also quickly constructed when the ortho group is H. These transformations undergo cascade thiophene construction/selective C3-position thiolation process, featuring simple operations, divergent synthesis, broad substrate scope, readily available starting materials, and valuable products. A novel plausible radical annulation process was proposed and validated by DFT calculations for the first time. A series of derivatizations about the thiophene (TBT) and disulfides were also well-represented.

Toll-like receptors (TLRs) respond to tributyltin chloride (TBT-Cl) exposure in the river pufferfish (Takifugu obscurus): Evidences for its toxic injury function.

Tributyltin chloride (TBT-Cl) residual in water body had become a noticeable ecological problem for aquatic ecosystems. Toll-like receptors (TLRs) are an ancient family of pattern recognition receptors that play key roles in detecting nonself antigens and immune system activation. In this study, we explored the effect of TBT-Cl exposure on four TLRs expression in river pufferfish, Takifugu obscurus. The four T. obscurus Toll-like receptors (To-TLRs) contained different types of domains such as leucine-rich repeats (LRRs), leucine-rich repeats, typical subfamily (LRR_TYP) and other special domains. The To-TLRs mRNA transcripts expressed in all tissues, also To-TLR2 was investigated with higher level in kidney, as well as To-TLR3 in kidney, while To-TLR18 in liver and To-TLR22 in intestine. After the acute and chronic exposure of TBT-Cl, To-TLR2 and To-TLR3 mRNA transcripts were significantly down-regulated in gill. However, To-TLR18 and To-TLR22 were significantly up-regulated in gill and liver. Moreover, the histology and immunohistochemistry (IHC) results showed the different injury degrees of TBT-Cl in liver and gill and implied the cytoplasm reorganization after TBT-Cl stress and the function of immunoregulation for To-TLRs to TBT-Cl exposure. All the results indicated that To-TLRs might involve in sensing and mediating innate immune responses caused by TBT-Cl for keeping detoxification homeostasis.

World Trade Organization: notification of sanitary and phytosanitary measures.

This paper provides an overview of the importance of transparency at the World Trade Organization, a basic principle that translates into notification obligations. In particular, the paper details the related obligations under the Agreement on the Application of Sanitary and Phytosanitary Measures, and how it applies to trade in animals and animal products.

Les auteurs offrent une vue d'ensemble du rôle joué par la transparence au sein de l'Organisation mondiale du commerce, principe de base qui se traduit par une obligation de notification. En particulier, ils précisent les obligations prévues en vertu de l'Accord sur l'application des mesures sanitaires et phytosanitaires et la manière dont ce principe s'applique aux échanges internationaux d'animaux et de produits d'origine animale.

Los autores explican la importancia que dentro de la Organización Mundial del Comercio reviste la transparencia, un principio básico que se traduce en obligaciones de notificación. En particular, describen en detalle las obligaciones que en este sentido impone el Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias y cómo se aplica dicho principio al comercio de animales y productos de origen animal.

Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism.

BACKGROUND/AIMS: Tributyltin (TBT) is an organotin (OTs) and biohazard organometallic pollutant. Recently our group has shown that TBT, even in very low doses, has deleterious effects on several tissues most likely due to its role as an endocrine-disrupting molecule. Other studies have confirmed that OT exposure could be responsible for neural, endocrine, and reproductive dysfunctions via in vitro and in vivo models. However, TBT effects on bone lack concise data despite the fact that bone turnover is regulated by endocrine molecules, such as parathormone (PTH), estrogen (E2), etc. Our group has already shown that TBT disrupts adrenal and female gonadal functions. METHODS: We studied the effects of TBT on bone metabolism and structure using DXA, microCT scan, and SEM. We also determined the calcium (Ca²âº) and phosphate (Pi) metabolism in TBT-treated rats as well as some biomarkers for bone formation and resorption. RESULTS: Surprisingly, we found that TBT leads to higher bone mineral density (BMD) although lesions in spinal bone were observed by either microCT scan or SEM. Biomarkers for bone resorption, such as the urinary deoxipyridinolines (DPD) excretion ratio was increased in TBT-treated animals versus mock-treated controls. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone formation and are also elevated suggesting that the bone matrix suffers from a higher turnover. Serum Ca²âº (total and ionized) do not changed by TBT treatment although hypercalciuria is observed. CONCLUSION: It is known that Sn atoms have three valence states (Sn²âº, Sn³âº, and Sn4⁺); hence, we hypothesized that Sn (more likely Sn²âº) could be competing with Ca²âº and/or Mg²âº in hydroxyapatite mineral matrix to disturb bone turnover. Further work is needed to confirm this hypothesis.

Chronic treatment with tributyltin induces sexually dimorphic alterations in the hypothalamic POMC system of adult mice.

Tributyltin (TBT), an antifouling agent found in boat paints, is a common contaminant of marine and freshwater ecosystems. It is rapidly absorbed by organic materials and accumulated in many aquatic animals. Human exposure may depend on ingestion of contaminated food or by indirect exposure from household items containing organotin compounds. TBT is defined as an endocrine disruptor compound (EDC) because it binds to androgen receptors. Moreover, it is also included on the list of metabolic disruptors. The brain is a known target of TBT and this compound interferes with the orexigenic system, inducing a strong decrease in NPY expression in the hypothalamus. In the present experiment, we investigated the effect of a chronic treatment with TBT on the mouse anorexigenic system in both sexes, to look at the pro-opiomelanocortin (POMC) expression in the paraventricular (PVN), dorsomedial (DMN), ventromedial (VMN), and arcuate (ARC) hypothalamic nuclei. The results show a sexually dimorphic effect of TBT on both systems. TBT induced a significant decrease of POMC-positive structures only in female mice in DMN, ARC, and in PVN for both sexes. Apparently, these results show that TBT may interfere with the anorexigenic system in hypothalamic areas involved in the control of food intake, by inhibiting POMC in a sexually dimorphic way. In conclusion, in addition to having a direct effect on fat tissue, the effects of TBT as metabolic disruptor, may be due to gender-specific actions on both orexigenic and anorexigenic hypothalamic systems.

Comparative transcriptomics analysis of the river pufferfish (Takifugu obscurus) by tributyltin exposure: Clues for revealing its toxic injury mechanism.

TBT residual in water had become a noticeable ecological problem for aquatic ecosystems. The river pufferfish (Takifugu obscurus) is a kind of an anadromous fish species and widely distributed in the East China Sea and the Yellow Sea. Because of the water contamination, the pufferfish wild resource had a sudden decline in recent years. Therefore, the study on the response of pufferfish to the TBT exposure may contribute to reveal toxic injury mechanism of T. obscurus under TBT exposure. In this study, the transcriptional library of T. obscurus liver and gill was constructed and sequenced by an improved Illumina HiseqX10 high-throughput sequencing platform under different concentrations of TBT acute stress. The blood cell numbers distinctly decreased after TBT exposure, showing the adverse effects of TBT invasion and self-adjusting ability of the pufferfish. The production of reactive oxygen species increased, demonstrating the oxidation resistance of T. obscurus when exposed to TBT. The obtained data were compared with the genome data of Takifugu rubripes and transcriptional resource database. On this basis, gene function annotation, analysis and classification were carried out by bioinformatics method, and differential genes related to toxic injury function were screened out. Meanwhile, new toxic related genes and related signal pathways were sought to provide new theoretical guidance for the pathogenesis of T. obscurus exposed to TBT. This study not only enriched the transcriptome data of T. obscurus under environmental stress, but also provided a new research method for the response mechanism of T. obscurus under the stimulation of environmental factors.

Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions, showing that they are as sensitive as molluscs, and for some species, even more sensitive. Concentrations in the range of 1 ng/L for water exposure (10 ng/g for whole-body burden) have been shown to elicit endocrine-type responses, whereas mortality occurs at water concentrations ten times higher. Current screening and assessment methodologies as compiled in the OECD CFEDTA are able to identify TBT as a potent endocrine disruptor with a high environmental risk for the original use pattern. If those approaches had been available when TBT was introduced to the market, it is likely that its use would have been regulated sooner, thus avoiding the detrimental effects on marine gastropod populations and communities as documented over several decades.

Pufferfish Saxitoxin and Tetrodotoxin Binding Protein (PSTBP) Analogues in the Blood Plasma of the Pufferfish Arothron nigropunctatus, A. hispidus, A. manilensis, and Chelonodon patoca.

Pufferfish saxitoxin and tetrodotoxin (TTX) binding protein (PSTBP) is a glycoprotein that we previously isolated from the blood plasma of the pufferfish Takifugu pardalis; this protein was also detected in seven species of the genus Takifugu. We proposed that PSTBP is a carrier protein for TTX in pufferfish; however, PSTBP had not yet been found in genera other than Takifugu. In this study, we investigated the presence of PSTBP-like proteins in the toxic pufferfish Arothron nigropunctatus, A. hispidus, A. manilensis, and Chelonodon patoca. On the basis of ultrafiltration experiments, TTX was found to be present and partially bound to proteins in the plasma of these pufferfish, and Western blot analyses with anti-PSTBP antibody revealed one or two bands per species. The observed decreases in molecular mass following deglycosylation with glycopeptidase F suggest that these positive proteins are glycoproteins. The molecular masses of the deglycosylated proteins detected in the three Arothron species were larger than that of PSTBP in the genus Takifugu, whereas the two bands detected in C. patoca had molecular masses similar to that of tributyltin-binding protein-2 (TBT-bp2). The N-terminal amino acid sequences of 23⁻29 residues of these detected proteins were all homologous with those of PSTBP and TBT-bp2.

Microbes a Tool for the Remediation of Organotin Pollution Determined by Static Headspace Gas Chromatography-Mass Spectrometry.

Tributyltin (TBT) is one of the most toxic anthropogenic compounds introduced into the marine environment. Despite its global ban in 2008, TBT is still a problem of great concern due to its high affinity for particulate matter, providing a direct and potentially persistent route of entry into benthic sediments. Bioremediation strategies may constitute an alternative approach to conventional physicochemical methods, benefiting from the microorganism's potential to metabolize anthropogenic compounds. In this work, a simple, precise and accurate static headspace gas chromatography method was developed to investigate the ability of TBT degrading microbes in sedimentary microcosms over a period of 120 days. The proposed method was validated for linearity, repeatability, accuracy, specificity, limit of detection and limit of quantification. The method was subsequently successfully applied for the detection and quantification of TBT and degradation compounds in sediment samples on day 0, 30, 60, 90 and 120 of the experiment employing the principles of green chemistry. On day 120 the concentration of TBT remaining in the microcosms ranged between 91.91 ng/g wet wt for the least effective microbial inoculant to 52.73 ng/g wet wt for the most effective microbial inoculant from a starting concentration of 100 ng/g wet wt.