• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.469-476
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• 2012

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, ${\alpha}$-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (${\alpha}$-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

• 한국식품영양과학회지
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• 제28권6호
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• pp.1349-1354
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• 1999

This study was carried out to investigate the protective effect of Korean red ginseng water extract (KRG WE) on clinical chemical parameters in male guinea pigs acutely exposed to 2,3,7,8 tetrachlorodibenzo p dioxin(TCDD). Forty male guinea pigs(200 $\pm$20g) were divided into 4 groups. Normal controls(group 1) received vehicle and saline; group 2(single TCDD treated) received TCDD(5 g/kg, single dose) intraperitoneally; group 3 received KRG WE(200mg/kg, i.p.) for 2 weeks from 1 week before TCDD exposure; group 4 received KRG WE for 1 week since the day of TCDD exposure. Increase in body weight was retarded greatly by TCDD exposure. Body weight of animals in group 2 was significantly decreased starting 2 days after TCDD exposure. However, body weight of animals in group 3 increased throughout the experimental period, although the increasing rate was slower than that of group 1. Decrease in body weight was not observed during the experimental period in group 4. Increases in blood glucose, amylase, lipase, total cholesterol, triglyceride, GOT, GPT, and LDH levels by TCDD intoxication were significantly attenuated by the KRG WE treatment(p<0.05). These results provide a strong evidence that Korean red ginseng might be a useful protective agent against TCDD, an endocrine disruptor.

• 한국식품위생안전성학회지
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• 제18권2호
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• pp.56-60
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• 2003

환경호르몬으로 독성이 강하기로 유명한 TCDD는 간을 포함한 각 조직에 손상을 주고, 내분비의 붕괴를 야기 시킨다. 본 연구는 TCDD로 처리한 rat의 간과 혈장을 사용하여, 어성초의 생화학적 효과를 연구하였다. TCDD를 투여한 지 일주일 후부터 어성초 200 mg/kg을 4주간 격일로 투여하고 TCON군과 NO군은 saline을 투여하였다. 혈청에서 total cholesterol, HDL-cholesterol, LDL-cholesterol, total lipid, triglyceride(TG)를 간조직중에서 MDA를 측정함으로써 과산화지질 활성도와 콜레스테롤의 양을 조사하였다. TCDD로 처치한 rat에 어성초 추출물을 투여했을 때, 과산화지질 및 콜레스테롤이 유의적인 수준으로 억제되었다.

• Journal of Ginseng Research
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• 제30권1호
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• pp.8-14
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• 2006

본 연구는 랫드에서 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD)로 유도된 급성독성에 대한 홍삼유출액으로부터 분리한 조사포닌의 방어효과를 조사하기 위해 수행되었다. 40마리의 웅성 랫드를 4군으로 나누어 정상군에 대해서는 TCDD의 운반체를, TCDD 단독투여군 (TT)에게는 TCDD($5{\mu}g/ml$)와 생리식염수를 1회 복강주사하였다. 한편, 조사포닌 투여군 (RGE-CS20, RGE-CS40)은 조사포닌을 각각 20 및 40 mg/kg,b.w/day의 용량으로 TCDD 투여 1주 전부터 총 4 주간 복강주사하였다. TCDD 단독투여군의 체중은 TCDD투여 1주째부터 유의하게 감소한 반면, 조사포닌 투여군은 TCDD 단독투여군에 비해 완만하기는 하지만 유의하게 증가하여 체중감소가 억제되었다. 조사포닌 투여군은 TCDD독성에 의해 증가한 TG, TC, LDL, AST ALT, $Fe^{2+}$ 함량은 감소시켰고, TCDD 독성에 의해 감소된 glucose, amylase, LDH, CK 활성을 증가시켜 혈액 임상화학지수를 유의하게 개선시키는 것으로 나타났다. 이상의 결과로부터 홍삼유출액으로부터 분리한 조사포닌은 TCDD에 의해 주도된 체중감소와 장기 기능저하에 대해서 현저한 방어효과를 나타낸다는 사실을 알 수 있었다.

• 한국환경보건학회지
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• 제35권4호
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• pp.259-268
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• 2009

This study was carried out to investigate the protective effect of Red Ginseng Saponins on 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced toxicities in guinea pigs ($200{\pm}10$ g). Normal control (NC) group guinea pigs ($200{\pm}10$ g) received vehicle and saline, while the TCDD-treated (TT) group was given water-extract (WE), saponin fraction (SF) and non-saponin fraction (NSF). Korean red ginseng fractions were administered from 1 week before TCDD-exposure for 4 weeks. Body weight loss and deteriorated clinical parameters related to sugar metabolism and liver function such as lipase and AST, respectively, these were significantly reduced by both saponin and non-saponin fractions. However, increase of lipase was attenuated by the saponin fraction in a dose-dependent manner. Only AST was affected by the saponin fraction. The results suggest that saponins are active substances in the Korean red ginseng water extract against TCDD induced toxicities in Guinea pigs.

• Toxicological Research
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• 제15권1호
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• pp.89-93
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• 1999

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is known to induce cytochrome p450 1A1 and to activate c-Src kinase and p21 Ras. This study examined the molecular interactions of adaptor proteins including Shc, Grb2, and Sos in rat primary hepatocytes and their relationship to the induction of CYP1A1 by TCDD. TCDD induced CYP1A1 level and EROD activity in a dose-dependent mode. Sos/Grb2 association isincreased by TCDDㅑㅜ a dose dependent mode. Tyrosine phosphorylated Shc, mainly p152, onloads to Grb2/Sos complex upon TCDD stimulation. The electrophoretic mobility shift of Sos is showed by TCDD. These results indicate that TCDD modulated the molecular interaction features of adaptor compoes proteins including Shc, Grb2, and Cnl in early signaling pathway of TCDD-mediated CYP 1A1 induction of rat primary hepatocyte.

• 생약학회지
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• 제32권2호통권125호
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• pp.121-127
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• 2001

The effect of bear bile on 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-induced hepatotoxicity was investigated in 6-week-old C57BL/6 male mice. Bear bile (100 mg/kg or 500 mg/kg) was administered orally daily for 4 weeks, respectively. From the second week, $10\;{\mu}g/kg$ of TCDD was administered to the bear bile-treated animals orally once a week for 3 weeks (a total of $30\;{\mu}g/kg$). There were no specific clinical findings and significant body weight changes in all groups. Although the livers in TCDD-treated mice appeared a severe hypertrophy and many necrotic foci, and changed to yellow-brown color in gross findings, these lesions were remarkably reduced by bear bile administration. The elevated serum activities of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase due to TCDD were significantly decreased by bear bile treatment (P<0.05). The lipid peroxidation induced by TCDD was significantly prevented by bear bile administration (P<0.05). In histological examinations, there were a moderate necrosis of hepatic cells around central veins, severe cytoplasmic vacuolizations, inflammatory cell infiltrations, and remarkable fatty changes in the liver of TCDD-treated animals. However, the lesions were dose-dependently inhibited by the bear bile treatments. These findings indicate that bear bile may have a protective effect against TCDD-induced hepatotoxicity in mice.

• Journal of Nutrition and Health
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• 제46권3호
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• pp.207-217
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• 2013

This study was conducted in order to investigate the effects of Artemisia capillaris (AC) extract on disorders of hepatic functions and lipid metabolism induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disrupter, using male rats (SD, five weeks old) for a period of three weeks. These 37 animals were divided into four groups. AC extract was added as 1.5% or 3% levels to basal diets, respectively. TCDD (40 ug/kg B.W) was administered by intraperitoneal injection into rats after a week from the beginning of the experiment. AC extract alleviated the increase of rat's relative liver weights induced by TCDD. Thymuses of all rats treated with TCDD were apparently shrunken by approximately 80%. Levels of white blood cells (WBC), red blood cells, hemoglobin, and hematocrits were significantly increased by treatment with TCDD, however, WBC tended to decrease by AC extract diets. In hepatic function, the elevation of glutamic oxalacetic transaminase activities by TCDD treatment was diminished by AC extract diets. Serum HDL-cholesterol levels were significantly elevated by AC extract diets. The apparent increase of triglyceride levels of rat livers induced by TCDD was significantly suppressed in the AC extract diet groups. Hepatic cytosolic catalase activities significantly decreased by treatment with TCDD showed a recovering trend by AC extract diets. In histochemical observation, the fat droplets and apoptosis of hepatocytes treated with TCDD were markedly alleviated by AC extract diets. These results indicated that AC could exert recovering effects on some disorders of hepatic functions, lipids metabolism, and antioxidant activities resulting from TCDD treatment.

• Toxicological Research
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• 제19권4호
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• pp.325-330
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• 2003

The effects of estrogen on apoptosis induced by 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD) were examined in cultured MCF-7 cells. TCDD stimulated apoptosis and inhibited the expression of bcl-2 gene in MCF-7 cells grown in the media supplemented with 10% fetal bovine serum. However, TCDD failed to induce apoptosis if cells were grown in the media deprived of all estrogen-like compounds. Removal of estrogen-like compounds from the growth media also led to the activation of bcl-2 gene expression in cells treated with TCDD. Combined treatment of estrogen with TCDD abrogated the binding of Aryl hydrocarbon Receptor (AhR)-TCDD complex to Dioxin response element (DRE) of bcl-2 gene leading to the inhibition of bcl-2 gene expression as well as stimulation of apoptosis. The present study suggests that the binding of estrogen receptor (ER)-estrogen complex to the estrogen responsive element (E) interferes with the binding of AhR- TCDD complex to the DRE and inhibits the bcl-2 expression.

• 대한의생명과학회지
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• 제7권4호
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• pp.197-203
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• 2001

This study was carried out to investigate the effect of crude ginseng saponin (CGS) on clinical pathological parameters in adult female guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A total of 80 guinea pigs (800$\pm$20 g) were divided into 8 groups: group 1 (normal control group) was given vehicle (com oil containing small amount of acetone and DMSO) and saline; group 2 (single TCDD-treated) received TCDD (1 $\mu\textrm{g}$/kg, i.p.) and saline (i.p.); groups 3 and 4 were administered CGS at daily i.p. doses of 10 and 20 mg/kg for 4 weeks, respectively; groups 5 and 6 were administered CGS (10 and 20 mg/kg, respectively) for 5 weeks starting 1 week before TCDD-exposure; groups 7 and 8 were administered CGS (10 and 20 mg/kg, respectively) for 3 weeks from 1 week after TCDD-exposure. CGS was prepared by Diaion HP-20 adsorption chromatography. Body weight of G2 was significantly decreased from the 2nd week after TCDD-exposure (p<0.01). Body weights of the CGS-treated groups were also decreased by TCDD-exposure, but the weight loss was greatly retarded compared with that of G2. Increase in blood glucose, amylase, lipase, total cholesterol. triglyceride, AST and LDL-cholisterol levels by TCDD exposure was significantly attenuated by the CGS-treatment (p<0.05). From these results, we found that saponin the main active ingredient of ginseng, played a protective role against TCDD-induced toxicity in not only male but female guinea pigs.