• Title/Summary/Keyword: 2,3,7,8-TCDD

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Involvement of Intracellular Ca2+-and PI3K-Dependent ERK Activation in TCDD-Induced Inhibition of Cell Proliferation in SK-N-SH Human Neuronal Cells

  • Yang, Seun-Ah;Lee, Yong-Soo;Jin, Da-Qing;Jung, Jae-Wook;Park, Byung-Chul;Lee, Yoon-Seok;Paek, Seung-Hwan;Jeong, Tae-Cheon;Choi, Han-Gon;Yong, Chul-Soon;Yoo, Bong-Kyu;Kim, Jung-Ae
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.78-83
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    • 2005
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) has previously shown to induce neurotoxicity through intracellular $Ca^{2+}$ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular $Ca^{2+}$ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD(10nM) rapidly increased the level of intracellular $Ca^{2+}$, which was completely blocked by the extracellular $Ca^{2+}$ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker. flufenamic acid (200 ${\mu}M$). However, pretreatment of the cells with dantrolene (25 ${\mu}M$) and TMB-8(10 ${\mu}M$), intracellular $Ca^{2+}$-release blockers, or a voltage-sensitive $Ca^{2+}$ channel blocker, varapamil (100 ${\mu}M$), failed to block the TCDD-induced $Ca^{2+}$ increase in the cells. In addition, TCDD induced a rapid and transient activation of phatidvlinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2(ERK1/2), which was ingnificantly blocked by the pretreatment with BAPTA, an intracellular $Ca^{2+}$ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular $Ca^{2+}$ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular $Ca^{2+}$ and PI3K-dependent activation of ERK 1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells.

Sample Pretreatment and HRGC/HRMS Analysis for Determination of Dioxins in Environmental Samples (환경시료 중 다이옥신류의 정량을 위한 시료전처리방법의 개선 및 고분해능 GC/MS 분석에 관한 연구 Ⅰ)

  • Kim, Jin Yeong;Jang, Yun Seok;Lee, Dae Un
    • Journal of the Korean Chemical Society
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    • v.38 no.11
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    • pp.819-826
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    • 1994
  • This study described a simple, rapid and cost effective analytical technique for the ultra-trace analysis of dioxins in environmental samples. Liquid-Liquid extraction methods were used for the initial extraction and enrichment of the analyte. Subsequent clean-up procedures were achieved by using strong cation exchanger, silica and Florisil cartridges. Extracts were analysed by HRGC/HRMS-SIM. The efficiency of these analytical methods was tested by recovery and selectivity for elimination of interferences such as phenols, pesticides and PCBs in each step. The mean recovery of 1,2,3,4-TCDD spiked at 10 ppt in sea water was about 92(${\pm}$1.6)%. This analytical method was applied to Kwangyang sea water and 4.5pg/L of 2,3,7,8-TCDD was determined.

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Effects of Saururus chinensis Baill on Glutathione and Antioxidative Activity Against TCDD-treated Rats (환경 Hormone에 대한 삼백초의 Glutathione 및 항산화 활성 효과)

  • Ha, Bae-Jin
    • Journal of Food Hygiene and Safety
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    • v.18 no.3
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    • pp.161-165
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    • 2003
  • The effects of Saururus chinensis Baill administration on the biochemical parameters of function in liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated rats were investigated. Saururus chinensis Baill (200mg/kg) was administered into rats intraperitoneally for four weeks, seven days after the injection of TCDD(1 ${\mu}g/kg$). We examined the antioxidative enzymatic activity by measuring the level of AST and ALT in serum and SOD, Catalase, GPx, GSH and GSSG in liver tissue of rats. STT group showed 70.7% of inhibitive effect in AST acrivity compared to TTA group. ALT level of STT group was decreased to the level of NTT group. SOD and Catalase in TTA group were lower than in NTT group, but SOD and Catalase in STT group were increased by 82% and 55.45% respectively compared to TTA group. GSH contents in STT group were 74.20% increased compared to TTA group. GSSG contents in STT group were 61.08% decreased compared to TTA group. These results suggest that Saururus Chinensis Baill has a potent hepathprotective effect against TCDD intoxicated rats.

Effects of Leucocyanidins on TCDD-Induced Lipid Peroxidation in Female Rat (흰쥐에서의 2,3,7,8-Tetrachlorodibenzo-p-Dioxine 유발 지질 과산화 반응에 대한 Leucocyanidins(Vitis vinifera L.)의 효과)

  • Jhee Ok-Hwa;Lee Joo-Won;Kim Shin-Hee;Won Hei-Dan;Kim Hyun-Jin;Park Yun-Young;Kang Min-Jeong;Park Sung-Kug;Om Ae-Sun;Back Seung-Sam;Kang Ju-Seop
    • The Korean Journal of Food And Nutrition
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    • v.18 no.4
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    • pp.295-301
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    • 2005
  • Effects of leucocyanidins on the level of serum lipids and lipid peroxidation was investigated in 2,3,7,8-tetrachlorodibenzo-p-dioxine(TCDD)-induced rat that were pretreated with leucocyanidins for 4 weeks. The rats were divided into five experimental groups that is leucocyanidins and low TCDD treated group(LTL, 0.1 ${\mu}\;g/kg$ TCDD), leucocyanidins treated high TCDD group(LTH, 10 ${\mu}\;g/kg$ TCDD), No leucocyanidins and low TCDD treated group(NTL, 0.1 ${\mu}\;g/kg$ TCDD) and no leucocyanidins and high TCDD treated group(NTL, 10 ${\mu}\;g/kg$ TCDD). Serum total cholesterol, LDL-cholesterol and triglyceride level were significantly decreased and HDL-cholesterol level significantly increased in leucocyanidins treated group. Serum MDA level was also significantly reduced in leucocyanidins treated group. These results suggest that pre-supplement of leucocyanidins prevented the degree of lipid peroxidation on TCDD induced rat.

Serum Concentration and Exposure History of Dioxins and Organochlorine Pesticides among Residents around the Camp Carroll Area (캠프캐럴 인근 주민에서 다이옥신류 및 유기염소계 농약의 혈중 농도 및 노출력)

  • Bae, Sang Geun;Kim, Geun-Bae;Cho, Yong-Sung;Lee, Yu-mi;Lee, Duk Hee;Yang, Wonho;Ju, Young-Su;Lee, Kwan;Min, Young-Sun;Lim, Hyun-Sul
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.26 no.3
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    • pp.277-285
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    • 2016
  • Objectives: This study was performed in order to evaluate whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could be detected among residents living near Camp Caroll in Waegwan and whether serum concentrations of dioxins, including 2,3,7,8-TCDD, and organochlorine pesticides (OCPs) are associated with length of residence. Methods: Study subjects totaled 113 (for dioxins) and 190 (for OCPs) adults who were selected from participants in a medical investigation. Serum concentrations of dioxins and OCPs were measured using HRGC/HRMS. Information on length of residence was obtained through questionnaires. Results: 2,3,7,8-TCDD was not detected in serum among all subjects. When length of residence was classified as a categorical variable, after adjusting for confounding variables, only residents living in Waegwan for 40 years or longer tended to have high total TEQ values and 2,3,4,7,8-PeCDF with marginal significances. There was no dose-response relation between length of residence and serum concentrations of these chemicals. In multiple regression models with continuous values of the length of residence, total TEQ value and 1,2,3,4,6,7,8-HpCDF were positively associated with length of residence. However, they explained about 3-5% of total variations of serum concentrations of these compounds, while age, consumption of fatty fish, body mass index, alcohol drinking, and cigarette smoking were main variables affecting serum concentrations of dioxins or OCPs. Conclusions: In the current study, high concentrations of certain compounds were mainly observed among persons who lived in Waegwan for at least for 40 years without a dose-response relation. Therefore, it seems difficult to conclude that length of residence meaningfully contributed to the current serum concentrations of dioxins or OCPs among residents in Waegwan. However, considering the half-life of 2,3,7,8-TCDD and indirect exposure routes, the limitations of the current study design should be considered in the interpretation of the study findings.

Prediction of Adsorption Isotherms and Diffusivity on Activated Carbon for Persistent Organic Pollutant(2,3,7,8-TCDD) (활성탄 위에서 잔류성 유기 오염물질(2,3,7,8-TCDD)의 등온 흡착식 및 확산계수 예측)

  • Lim, Young-Il;Son, Hae-Jeong;Lee, Ohsung;Nam, Kyong-Soo;Yoo, Kyoung-Seun
    • Korean Chemical Engineering Research
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    • v.47 no.6
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    • pp.747-754
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    • 2009
  • In this study, adsorption isotherms of o-DCB(ortho-dichlorobenzene) on an activated carbon heated at $1000^{\circ}C$ for 24 hours were obtained by experiment and were predicted by using molecular simulation. The initial molecular structure of the activated carbon was designed on the basis of its molecular formula and functional groups ratio measured experimentally. Then, the molecular structure was optimized using the COMPASS(condensed-phase optimized molecular potentials for atomistic simulation studies) force field. The particle porosity, specific surface area, and particle density obtained from the optimized molecular structure of activated carbon were compared with those experimental data. The errors between experimental data and simulation results of the particle porosity, specific surface area, and particle density were shown as 7.6, 3.8, and 2.8%, respectively. Adsorption isotherms constants of o-DCB are calculated by the GCMC(grand canonical Monte Carlo) method in the optimized molecular structure of activated carbon. The simulation result of the adsorption isotherms showed an error of under 3%, compared to that of experimental data. Adsorption isotherms, adsorption heat and pore diffusivity of 2,3,7,8-TCDD(tetrachlorodibenzo-p-dioxin) was finally obtained in the same molecular structure of the activated carbon as used for o-DCB. Thus, adsorption characteristics of persistent organic pollutants on activated carbon, which are not easy to experimentally evaluate, are predicted by the molecular simulation.

The Effects of Gobonyangjeonbang Administration on Reproductive Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Rats. (고본양정방 투여가 TCDD 유도 랫드의 생식독성에 미치는 영향)

  • OH, Ji Hye;Yang, Dong Hyun;Park, Un kyu;Cho, Chung Sik;Hwang, Seock Yeon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.4
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    • pp.504-512
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    • 2021
  • Sperm formation disorders and sperm quality degradation comprises the largest proportion of male infertility caused by TCDD. To solve this problem, this study examined the effects of Gobonyangjeonbang oriental medicine prescription on the endocrine function and reproductive toxicity-related indicators in rat-induced TCDD-induced reproductive. Male SD rats were divided into five groups of seven animals and tested. The normal control group was administered the vehicle and saline, the TCDD alone group was administered intraperitoneally with TCDD (2 ㎍/kg, weeks) and physiological saline, and the test group was administered orally by dividing GYB (75, 150, and 300 mg/kg) into three concentrations for six weeks. Weight loss was observed in all groups administered TCDD. Regarding the hormonal changes, a significant decrease in free testosterone was observed in the GYB 300 mg/kg group (p<0.01). In addition, some of the germ cell destruction, seminiferous tubular atrophy, and decrease in sperm count was improved in a concentration-dependent manner in the testicular tissue of the GYB-treated group. In addition, Johnsen's score and serotoli cell index (SCI) were improved in a concentration-dependent manner (p<0.05). Overall, GYB can be used in drug therapy rather than medical procedures to solve male infertility in the future.

Effect of nitric oxide on the cyplal gene expression

  • Kim, Ji E.;Jung Y. Bae;Yhun Y. Sheen
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.141-141
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    • 1998
  • In order to study the effect of nitric oxide on the regulation of mouse cyplal expression, 5' flanking DNA of mouse cytochrome P450 lal was cloned into pGL3 basic vector encoding luciferase gene. pcyplal-Luc was transfected into Hepa I cells and various chemicals were treated. Luciferase activity was stimulated 1000 folds over that of control by TCDD (2,3,7,8-tetrachloro-p-dioxin) treatment and this stimulation was dose dependent. When SNP (sodium nitroprusside) which donates nitric oxide was administrated, this stimulatory effect of TCDD on luciferase activity was decreased. And LPS (lipopolysaccharide) which is an iNOS (inducible nitric oxide synthase) inducer also decreased the stimulatory effect of TCDD on luciferase. And iNOS inhibitor N$\^$G/-nitro-ι-arginine + TCDD treatment increased the stimulation effect of TCDD and this effect was abolished when ι-arginine was added to N$\^$G/-nitro-ι-arginine + TCDD treatment. When N$\^$G/-nitro-ι-arginine was concomitantly administrated with SNP or LPS to confirm the effect of nitric oxide, the inhibitory effect of SNP or LPS was abolished. These data strongly suggest that nitric oxide might be an inhibitory regulator on the cytochrome P450 lal gene expression in Hepa cells.

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