The Experts below are selected from a list of 711 Experts worldwide ranked by ideXlab platform
Liu Jiyan - One of the best experts on this subject based on the ideXlab platform.
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effects of sublethal levels of Tributyltin Chloride in a new toxicity test organism the chinese rare minnow gobiocypris rarus
Archives of Environmental Contamination and Toxicology, 2002Co-Authors: Zhou Qunfang, Jiang Guibin, Liu JiyanAbstract:A newly developed toxicity test organism, the Chinese rare minnow (Gobiocypris rarus), which has similar merits to some common experimental fishes and could become a standardized test species for China, was used in a short-term study with emphasis on accumulation in fish muscles and cytological effects of sublethal concentrations of tri-n-butyltin Chloride (TBT). The 1-year-old fish were exposed for 1 or 2 weeks to a concentration range of 50 to 5,000 ng TBT/L in static systems. Hepatosomatic Index (HSI) and Gonad Somatic Index (GSI) sensitively showed the adverse effects of TBT to the fish. Compared with the nominal TBT concentrations in water phase, 459-(5,000 ng TBT/L, 1 week) to 4,065- (50 ng TBT/L, 2 weeks)-fold higher concentrations of butyltin species were detected in the corresponding exposure fish muscle. Contaminations of TBT in muscle tissue increased with both the exposure levels and exposure time. The cellular pathological effects in the liver were studied. These included vacuoles with increasing number and size, swelling of mitochondria, abnormal nuclei, and decreases of rough endoplasmic reticulum cisternaes. The results confirmed that the Chinese rare minnow (G. rarus) could be utilized as a useful species to evaluate water toxicity in the laboratory.
Flora A. Milton - One of the best experts on this subject based on the ideXlab platform.
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Dibutyltin Compounds Effects on PPARγ/RXRα Activity, Adipogenesis, and Inflammation in Mammalians Cells.
Frontiers in Pharmacology, 2017Co-Authors: Flora A. Milton, Mariella G. Lacerda, Simone B. P. Sinoti, Pedro G. Mesquita, Dileesh Prakasan, Michella S. Coelho, Caroline L. De Lima, Alexandre G. Martini, Gabriela T. Pazzine, Maria De F. BorinAbstract:Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is Tributyltin Chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin Chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, diChloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to Tributyltin Chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, diChloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike Tributyltin Chloride, which is a full agonist of RXRα, dibutyltins diChloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts Tributyltin Chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and Tributyltin Chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins diChloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, Tributyltin Chloride and dibutyltin dilaurate reduced LPS-stimulated TNFα expression. Our findings indicate that dibutyltins diacetate, diChloride, dilaurate, and maleate are PPARγ partial agonists and that dibutyltins diChloride and dilaurate are also partial RXRα agonists. Furthermore, dibutyltins induce adipogenesis in a PPARγ-dependent manner and repress inflammatory genes in 3T3-L1 and RAW 264.7 cells. Although dibutyltins display some partial PPARγ/RXRα agonistic effects, the translation of cell-based results assays into in vivo effects on inflammation and insulin resistance is not entirely known. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the actions of organostanic compounds in whole-body context.
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dibutyltin compounds effects on pparγ rxrα activity adipogenesis and inflammation in mammalians cells
Frontiers in Pharmacology, 2017Co-Authors: Flora A. Milton, Mariella G. Lacerda, Simone B. P. Sinoti, Pedro G. Mesquita, Dileesh Prakasan, Michella S. Coelho, Caroline L. De Lima, Alexandre G. Martini, Gabriela T. PazzineAbstract:Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is Tributyltin Chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin Chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, diChloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to Tributyltin Chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, diChloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike Tributyltin Chloride, which is a full agonist of RXRα, dibutyltins diChloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts Tributyltin Chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and Tributyltin Chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins diChloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, Tributyltin Chloride and dibutyltin dilaurate reduced LPS-stimulated TNFα expression. Our findings indicate that dibutyltins diacetate, diChloride, dilaurate, and maleate are PPARγ partial agonists and that dibutyltins diChloride and dilaurate are also partial RXRα agonists. Furthermore, dibutyltins induce adipogenesis in a PPARγ-dependent manner and repress inflammatory genes in 3T3-L1 and RAW 264.7 cells. Although dibutyltins display some partial PPARγ/RXRα agonistic effects, the translation of cell-based results assays into in vivo effects on inflammation and insulin resistance is not entirely known. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the actions of organostanic compounds in whole-body context.
Bruce Blumberg - One of the best experts on this subject based on the ideXlab platform.
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The environmental obesogen Tributyltin Chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes.
The Journal of steroid biochemistry and molecular biology, 2011Co-Authors: John Ycaza, Bruce BlumbergAbstract:Obesogens are chemicals that predispose exposed individuals to weight gain and obesity by increasing the number of fat cells, storage of fats into existing cells, altering metabolic rates, or disturbing the regulation of appetite and satiety. Tributyltin exposure causes differentiation of multipotent stromal stem cells (MSCs) into adipocytes; prenatal TBT exposure leads to epigenetic changes in the stem cell compartment that favor the production of adipocytes at the expense of bone, in vivo. While it is known that TBT acts through peroxisome proliferator activated receptor gamma to induce adipogenesis in MSCs, the data in 3T3-L1 preadipocytes are controversial. Here we show that TBT can activate the RXR-PPARγ heterodimer even in the presence of the PPARγ antagonist GW9662. We found that GW9662 has a 10-fold shorter half-life in cell culture than do PPARγ activators such as rosiglitazone (ROSI), accounting for previous observations that GW9662 did not inhibit TBT-mediated adipogenesis. When the culture conditions are adjusted to compensate for the short half-life of GW9662, we found that TBT induces adipogenesis, triglyceride storage and the expression of adipogenic marker genes in 3T3-L1 cells in a PPARγ-dependent manner. Our results are broadly applicable to the study of obesogen action and indicate that ligand stability is an important consideration in the design and interpretation of adipogenesis assays.
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Taisen Iguchi1,2, Yoshinao Katsu1,2,
2007Co-Authors: Toshihiro Horiguchi, Bruce Blumberg, Hajime Watanabe, Yasuhiko OhtaAbstract:The persistent and ubiquitous environmental conta-minant, Tributyltin Chloride (TBT), induces not only imposex in gastropods but also the differentiation of adipocytes in vitro and increases adipose mass in vivo in vertebrates. TBT is a nanomolar affinity lig-and for retinoid X receptor (RXR) in the rock shell (Thais clavigera) and for both the RXR and the peroxisome proliferator activated receptor γ (PPARγ) in the amphibian (Xenopus laevis), mouse, and hu-man. The molecular mechanisms underlying induc-tion of imposex by TBT have not been clarified, th-ough several hypotheses are proposed. TBT pro-motes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo primarily through activa-tion of RXR and PPARγ. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumula-tion in adipose depots, liver, and testis of neonate mice and results in increased adipose mass in adults. In X. laevis, ectopic adipocytes form in and around gonadal tissues following organotin, RXR or PPARγ ligand exposure. TBT represents the first example of an environmental endocrine disrupter that promotes adverse effects from gastropods to mammals
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endocrine disrupting organotin compounds are potent inducers of adipogenesis in vertebrates
Molecular Endocrinology, 2006Co-Authors: Felix Grun, Hajime Watanabe, Zamaneh Zamanian, Lauren Maeda, Kayo Arima, Ryan Cubacha, David M Gardiner, Jun Kanno, Taisen Iguchi, Bruce BlumbergAbstract:Dietary and xenobiotic compounds can disrupt endocrine signaling, particularly of steroid receptors and sexual differentiation. Evidence is also mounting that implicates environmental agents in the growing epidemic of obesity. Despite a long-standing interest in such compounds, their identity has remained elusive. Here we show that the persistent and ubiquitous environmental contaminant, Tributyltin Chloride (TBT), induces the differentiation of adipocytes in vitro and increases adipose mass in vivo. TBT is a dual, nanomolar affinity ligand for both the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor γ (PPARγ). TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumulation in adipose depots, liver, and testis of neonate mice and results in increased epididymal adipose mass in adults. In the amphibian Xenopus laevis, ectopic a...
Zhou Qunfang - One of the best experts on this subject based on the ideXlab platform.
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effects of sublethal levels of Tributyltin Chloride in a new toxicity test organism the chinese rare minnow gobiocypris rarus
Archives of Environmental Contamination and Toxicology, 2002Co-Authors: Zhou Qunfang, Jiang Guibin, Liu JiyanAbstract:A newly developed toxicity test organism, the Chinese rare minnow (Gobiocypris rarus), which has similar merits to some common experimental fishes and could become a standardized test species for China, was used in a short-term study with emphasis on accumulation in fish muscles and cytological effects of sublethal concentrations of tri-n-butyltin Chloride (TBT). The 1-year-old fish were exposed for 1 or 2 weeks to a concentration range of 50 to 5,000 ng TBT/L in static systems. Hepatosomatic Index (HSI) and Gonad Somatic Index (GSI) sensitively showed the adverse effects of TBT to the fish. Compared with the nominal TBT concentrations in water phase, 459-(5,000 ng TBT/L, 1 week) to 4,065- (50 ng TBT/L, 2 weeks)-fold higher concentrations of butyltin species were detected in the corresponding exposure fish muscle. Contaminations of TBT in muscle tissue increased with both the exposure levels and exposure time. The cellular pathological effects in the liver were studied. These included vacuoles with increasing number and size, swelling of mitochondria, abnormal nuclei, and decreases of rough endoplasmic reticulum cisternaes. The results confirmed that the Chinese rare minnow (G. rarus) could be utilized as a useful species to evaluate water toxicity in the laboratory.
Gabriela T. Pazzine - One of the best experts on this subject based on the ideXlab platform.
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Dibutyltin Compounds Effects on PPARγ/RXRα Activity, Adipogenesis, and Inflammation in Mammalians Cells.
Frontiers in Pharmacology, 2017Co-Authors: Flora A. Milton, Mariella G. Lacerda, Simone B. P. Sinoti, Pedro G. Mesquita, Dileesh Prakasan, Michella S. Coelho, Caroline L. De Lima, Alexandre G. Martini, Gabriela T. Pazzine, Maria De F. BorinAbstract:Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is Tributyltin Chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin Chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, diChloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to Tributyltin Chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, diChloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike Tributyltin Chloride, which is a full agonist of RXRα, dibutyltins diChloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts Tributyltin Chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and Tributyltin Chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins diChloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, Tributyltin Chloride and dibutyltin dilaurate reduced LPS-stimulated TNFα expression. Our findings indicate that dibutyltins diacetate, diChloride, dilaurate, and maleate are PPARγ partial agonists and that dibutyltins diChloride and dilaurate are also partial RXRα agonists. Furthermore, dibutyltins induce adipogenesis in a PPARγ-dependent manner and repress inflammatory genes in 3T3-L1 and RAW 264.7 cells. Although dibutyltins display some partial PPARγ/RXRα agonistic effects, the translation of cell-based results assays into in vivo effects on inflammation and insulin resistance is not entirely known. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the actions of organostanic compounds in whole-body context.
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dibutyltin compounds effects on pparγ rxrα activity adipogenesis and inflammation in mammalians cells
Frontiers in Pharmacology, 2017Co-Authors: Flora A. Milton, Mariella G. Lacerda, Simone B. P. Sinoti, Pedro G. Mesquita, Dileesh Prakasan, Michella S. Coelho, Caroline L. De Lima, Alexandre G. Martini, Gabriela T. PazzineAbstract:Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is Tributyltin Chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin Chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, diChloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to Tributyltin Chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, diChloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike Tributyltin Chloride, which is a full agonist of RXRα, dibutyltins diChloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts Tributyltin Chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and Tributyltin Chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins diChloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, Tributyltin Chloride and dibutyltin dilaurate reduced LPS-stimulated TNFα expression. Our findings indicate that dibutyltins diacetate, diChloride, dilaurate, and maleate are PPARγ partial agonists and that dibutyltins diChloride and dilaurate are also partial RXRα agonists. Furthermore, dibutyltins induce adipogenesis in a PPARγ-dependent manner and repress inflammatory genes in 3T3-L1 and RAW 264.7 cells. Although dibutyltins display some partial PPARγ/RXRα agonistic effects, the translation of cell-based results assays into in vivo effects on inflammation and insulin resistance is not entirely known. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the actions of organostanic compounds in whole-body context.
