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Effect of environmental pollutants on obesity parameters in vitro
Abstracts / Toxicology Letters 211S (2012) S43–S216
endpoint change in sex ratio and does not cause any significant change in the VTG levels when exposed to adult stages of zebra fish, it was concluded that the plasticizer does not display endocrine disrupting effects in zebra fish. doi:10.1016/j.toxlet.2012.03.343
P11-40 Effect of environmental pollutants on obesity parameters in vitro Camilla Taxvig, Julie Boberg, Christine Nellemann, Anne Marie Vinggaard National Food Institute, DTU, Denmark Recent data link exposure to endocrine disrupting chemicals during development with adverse health effects such as obesity and metabolic disorders. Data from animal and human studies show an association between exposure to different endocrine disrupting chemicals and development of obesity. Adipose tissue growth involves formation of new adipocytes from precursor cells, as well as increase in adipocyte size. One transcription factor family shown to play a key role in adipocyte differentiation is the peroxisome proliferator activated receptor (PPAR) family, specifically PPAR␥. Purpose: We have studied 12 chemicals representing various chemical classes and mechanisms of action: bisphenol A, hexachlorobenzene, perfluorooctanoic acid (PFOA), 1,1dichloro-2,2-bis(p-chlorophenyl)-ethylene (4,4-DDE), PCB 153, mancozeb, prochloraz, chlorpyrifos, deltamethrin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mono-(2-ethylhexyl) phthalate (MEHP), and butylparaben. Methods: They were examined for their potential effect on adipocyte differentiation and subsequent lipid accumulation in 3T3-L1 cells, as well as their effect on the release of adipocyte secreted hormones, and their ability to activate murine PPAR␣ and PPAR␥ in transactivation assays. Results and conclusion: Results show that the majority of chemicals have the ability to affect adipocyte differentiation in 3T3-L1 cells. Among the positive findings were butylparaben, PCB153, MEHP, and bisphenol A. Overall the results support the involvement of PPARs but also other mechanisms of action in the process of chemically-induced adipogenesis and lipid accumulation. Additionally work is in progress to study effects in human adipocytes. Acknowledgment: This work was supported by the Danish Agency for Science Technology and Innovation (grant no. FI J. nr. 2101-08-0058) doi:10.1016/j.toxlet.2012.03.344
P11-41 Neuroinflammation-induced by Ochratoxin A: Proteomic and morphological approaches Florianne Tschudi-Monnet 1 , Jenny Sandström von Tobel 1 , Paola Antinori 2 , Robin Rosset 3 , Marie-Gabrielle Zurich 1 , Alex Scherl 2 1
UNIL, SCAHT, Switzerland, 2 UNIGE, SCAHT, Switzerland, 3 UNIL, Switzerland
sion and phosphorylation, as marker of axonal integrity. Proteomic analyses of homogenates showed the quantitative modifications of a restricted number of proteins. Some are a signature for oxidative stress and neuroinflammation. The proteins detected in media suggested cytoskeleton instability. These results are in good agreement with morphological observations and quantification of mRNA expression of specific genes: OTA caused a dose-dependent shift of neuroprotective phenotype of microglial cells (arginase+) towards a macrophagic stage (ED1+). This was accompanied by a time and dose-dependent increase in the pro-inflammatory cytokines (IL1, TNF-␣, and IL-6) and the chemokine GRO, and a decrease in the anti-inflammatory cytokines (IL-4, IL-10). Hsp 32 mRNA expression increased with exposure time. At the neuronal level, no significant decrease of the mRNA expression of NF-H was observed. But at the protein level a decrease in the immunoreactivity of the nonphosphorylated form of NF-H was observed after 10 day exposure to OTA 2 and 10 nM. The staining for the phosphorylated form of NF-H was decreased only after 2 nM of OTA. These results showed that cytoskeleton instability and neuroinflammation are triggered by OTA exposure. However, the temporal cascade of OTA-induced adverse effects remains to be established. doi:10.1016/j.toxlet.2012.03.345
P11-42 An assessment of risk due to lead exposure in Firozabad Glass Industry, India Nrashant Singh, Nrashant Singh, Narendra Raghav, Ajay Agarwal S. N. Medical College, Agra, India As a result of man’s actions, lead (Pb) has become the most widely dispersed toxic metal in the environment. Glass industry is very old industry in India. Glass used for optical and decorative purposes contains Pb in place of calcium to increase the refractive index and lowers the viscosity of glass. Lead glass contains 18–40 wt.% lead (II)oxide (PbO), while lead-crystal glass, contains a minimum of 24% PbO which is responsible to cause deleterious health effects to workers. The present study was undertaken to assess the risk due to lead exposure and biological monitoring of workers involved in glass industry, Firozabad, India. Study consist of each 100 exposed and control subjects from similar socio-economic environments. The findings of present work showed that Blood lead levels (BLL) were higher than the permissible limit (30 g/dl) set by OSHA for occupational workers. Pb concentration in glass industry workers is significantly higher in comparison to control subjects. Elevated BLL in exposed subjects significantly inhibited the delta-aminolevulinic acid dehydratase synthesis in comparison to controls. Biomarkers of oxidative stress such as lipid-peroxidation, superoxide-dismutase, catalase and reduced-glutathione were significantly altered by elevated BLL in exposed subjects. The results of present study suggests that elevated BLL causes the negative health effects by impairment in antioxidant defense system or increased free radicals generation. In addition, we emphasize the need of regular exposure monitoring, and risk assessment especially estimated risk in future at certain level of exposure may help in the reduction in further exposure of Pb. doi:10.1016/j.toxlet.2012.03.346
Aggregating rat brain cell cultures were exposed to ochratoxin A (OTA) (2-10 nM) for 2 and 10 days. Homogenates and culture media were assayed for proteomic. In parallel, microglial reactivity and cytokine mRNA expression were measured as markers of neuroinflammation, hsp32 mRNA expression as marker of cellular stress, and neurofilaments of high molecular weight (NF-H) expres-
S91
endpoint change in sex ratio and does not cause any significant change in the VTG levels when exposed to adult stages of zebra fish, it was concluded that the plasticizer does not display endocrine disrupting effects in zebra fish. doi:10.1016/j.toxlet.2012.03.343
P11-40 Effect of environmental pollutants on obesity parameters in vitro Camilla Taxvig, Julie Boberg, Christine Nellemann, Anne Marie Vinggaard National Food Institute, DTU, Denmark Recent data link exposure to endocrine disrupting chemicals during development with adverse health effects such as obesity and metabolic disorders. Data from animal and human studies show an association between exposure to different endocrine disrupting chemicals and development of obesity. Adipose tissue growth involves formation of new adipocytes from precursor cells, as well as increase in adipocyte size. One transcription factor family shown to play a key role in adipocyte differentiation is the peroxisome proliferator activated receptor (PPAR) family, specifically PPAR␥. Purpose: We have studied 12 chemicals representing various chemical classes and mechanisms of action: bisphenol A, hexachlorobenzene, perfluorooctanoic acid (PFOA), 1,1dichloro-2,2-bis(p-chlorophenyl)-ethylene (4,4-DDE), PCB 153, mancozeb, prochloraz, chlorpyrifos, deltamethrin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mono-(2-ethylhexyl) phthalate (MEHP), and butylparaben. Methods: They were examined for their potential effect on adipocyte differentiation and subsequent lipid accumulation in 3T3-L1 cells, as well as their effect on the release of adipocyte secreted hormones, and their ability to activate murine PPAR␣ and PPAR␥ in transactivation assays. Results and conclusion: Results show that the majority of chemicals have the ability to affect adipocyte differentiation in 3T3-L1 cells. Among the positive findings were butylparaben, PCB153, MEHP, and bisphenol A. Overall the results support the involvement of PPARs but also other mechanisms of action in the process of chemically-induced adipogenesis and lipid accumulation. Additionally work is in progress to study effects in human adipocytes. Acknowledgment: This work was supported by the Danish Agency for Science Technology and Innovation (grant no. FI J. nr. 2101-08-0058) doi:10.1016/j.toxlet.2012.03.344
P11-41 Neuroinflammation-induced by Ochratoxin A: Proteomic and morphological approaches Florianne Tschudi-Monnet 1 , Jenny Sandström von Tobel 1 , Paola Antinori 2 , Robin Rosset 3 , Marie-Gabrielle Zurich 1 , Alex Scherl 2 1
UNIL, SCAHT, Switzerland, 2 UNIGE, SCAHT, Switzerland, 3 UNIL, Switzerland
sion and phosphorylation, as marker of axonal integrity. Proteomic analyses of homogenates showed the quantitative modifications of a restricted number of proteins. Some are a signature for oxidative stress and neuroinflammation. The proteins detected in media suggested cytoskeleton instability. These results are in good agreement with morphological observations and quantification of mRNA expression of specific genes: OTA caused a dose-dependent shift of neuroprotective phenotype of microglial cells (arginase+) towards a macrophagic stage (ED1+). This was accompanied by a time and dose-dependent increase in the pro-inflammatory cytokines (IL1, TNF-␣, and IL-6) and the chemokine GRO, and a decrease in the anti-inflammatory cytokines (IL-4, IL-10). Hsp 32 mRNA expression increased with exposure time. At the neuronal level, no significant decrease of the mRNA expression of NF-H was observed. But at the protein level a decrease in the immunoreactivity of the nonphosphorylated form of NF-H was observed after 10 day exposure to OTA 2 and 10 nM. The staining for the phosphorylated form of NF-H was decreased only after 2 nM of OTA. These results showed that cytoskeleton instability and neuroinflammation are triggered by OTA exposure. However, the temporal cascade of OTA-induced adverse effects remains to be established. doi:10.1016/j.toxlet.2012.03.345
P11-42 An assessment of risk due to lead exposure in Firozabad Glass Industry, India Nrashant Singh, Nrashant Singh, Narendra Raghav, Ajay Agarwal S. N. Medical College, Agra, India As a result of man’s actions, lead (Pb) has become the most widely dispersed toxic metal in the environment. Glass industry is very old industry in India. Glass used for optical and decorative purposes contains Pb in place of calcium to increase the refractive index and lowers the viscosity of glass. Lead glass contains 18–40 wt.% lead (II)oxide (PbO), while lead-crystal glass, contains a minimum of 24% PbO which is responsible to cause deleterious health effects to workers. The present study was undertaken to assess the risk due to lead exposure and biological monitoring of workers involved in glass industry, Firozabad, India. Study consist of each 100 exposed and control subjects from similar socio-economic environments. The findings of present work showed that Blood lead levels (BLL) were higher than the permissible limit (30 g/dl) set by OSHA for occupational workers. Pb concentration in glass industry workers is significantly higher in comparison to control subjects. Elevated BLL in exposed subjects significantly inhibited the delta-aminolevulinic acid dehydratase synthesis in comparison to controls. Biomarkers of oxidative stress such as lipid-peroxidation, superoxide-dismutase, catalase and reduced-glutathione were significantly altered by elevated BLL in exposed subjects. The results of present study suggests that elevated BLL causes the negative health effects by impairment in antioxidant defense system or increased free radicals generation. In addition, we emphasize the need of regular exposure monitoring, and risk assessment especially estimated risk in future at certain level of exposure may help in the reduction in further exposure of Pb. doi:10.1016/j.toxlet.2012.03.346
Aggregating rat brain cell cultures were exposed to ochratoxin A (OTA) (2-10 nM) for 2 and 10 days. Homogenates and culture media were assayed for proteomic. In parallel, microglial reactivity and cytokine mRNA expression were measured as markers of neuroinflammation, hsp32 mRNA expression as marker of cellular stress, and neurofilaments of high molecular weight (NF-H) expres-
S91