• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.471-479
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• 2012

This study was conducted to investigate the effects of various levels of chitosan oligomer (CO) molecular weight on the disorders of lipid metabolism and immune-related factors induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), that is a endocrine disrupter, using adult male rats (SD) for 3 weeks. These 40 animals were divided into five groups. Three kinds of CO were used by molecular weight (MW) (less than 1000, 1000~3000, and 5000~10000) and added 4% to basal diets respectively. TCDD (40 ${\mu}g$/kg B.W) was intraperitoneally injected into rats at the beginning of the experiment. The relative weights of the livers were increased in all rats treated with TCDD, and the brain and testis weights were increased in all CO diet groups, compared to the control and TCDD groups. The levels of white blood cells (WBC) and red blood cells (RBC), hemoglobin, hematocrits (HCT), and platelets were significantly lowered by treating TCDD. By the way, RBC and HCT tended to recover by CO diets. The elevation of serum total and HDL cholesterol levels induced by TCDD treatment was significantly reduced by CO (5000~10000 MW) diets. The apparent increasing of the total lipid, cholesterol, and triglyceride levels of rat livers induced by TCDD was tended to be suppressed in those fed CO diets. Especially, diets with less than 1000 MW significantly diminished liver triglycerides. The levels of serum immunoglobulin (Ig) A, IgG1 and IgM were significantly high in rats fed CO (5000~10000 MW) diets. The decreasing levels of IgE by treatment with TCDD tended to recover all the CO diet groups to the level of control group. In histochemical observation, the fat droplets and apoptosis of liver due to TCDD treatment were markedly alleviated in all CO diet groups. These results indicated that CO, though not regular according to molecular weight, can exert improving effects on lipid accumulation, hepatocytic disorders, abnormal blood cells, and some immunoglobulins induced by TCDD.

• Journal of Ginseng Research
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• v.32 no.4
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• pp.382-389
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• 2008

To achieve a better understanding of protective effects of water extracts of Panax ginseng against TCDD-induced toxicities, we monitored physiological and clinical changes in rat for 4 weeks after administrations of each Panax Ginseng extract or TCDD, and co-administration of the two materials. For this study, 120 male Sprague-Dawley (SD) rats weighing 190-210 g each (8 weeks old) were divided into four groups: TCDD-administered, co-administered group with TCDD and ginseng extract, ginseng extract-administered, and control group. The TCDD-administered group received single dose of TCDD in a corn oil vehicle ($25\;{\mu}g/kg$ body weight) by intraperitoneal administration on Day 1. The Panax ginseng extracts-administered group received intraperitoneally 100 mg/kg body weight every other day for one month. For the co-administered group with TCDD and ginseng extracts, Panax ginseng extracts were intraperitoneally administered to rats at 100 mg/kg body weight every other day for one month after a single intraperitoneal dose of $25\;{\mu}g$ of TCDD/kg body weight on Day 1. Panax ginseng extracts attenuated the mortality induced by TCDD administration. The extracts also slightly attenuated the TCDD-induced body weight loss. Administration of TCDD alone increased liver weight at 2, 5, and 16 days after administration of TCDD. Administration of Panax ginseng extracts rather decreased liver weight through whole the experimental period, but which was statistically insignificant. Administration of TCDD alone at $25\;{\mu}g/kg$ body weight increased both serum enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at 32 days, indicating that liver damage occurred maximally at that time. Ginseng extract administration caused insignificant changes in serum ALT, but gradually decreased in AST as the exposure time increased. Coadministration of TCDD and ginseng extracts caused serum AST activity to significant recovery to normal value at 16 days and 32 days after exposure to TCDD. The extracts also significantly decreased the TCDD-induced ALT activity after 16 days of TCDD administration. These results suggest that Panax ginseng extracts may possess a protective effect against TCDD-induced toxicities including hepatotoxicity in rats.

• Journal of Ginseng Research
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• v.30 no.1
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• pp.8-14
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• 2006

This study was carried out to investigate the protective effect of crude saponin from red ginseng efflux (RGE-CS) on biochemical parameters in male rats acutely exposed to 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin (TCDD). Forty male rats ($200{\pm}20g$) were divided into 4 groups. Normal control group (NC) received vehicle and saline; only TCDD-treated group (TT) received TCDD ($5{\mu}g/kg$, single dose) intrperitoneally; RGE-CS 20 received 20 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure; RGE-CS 40 also received 40 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure. Body weight of TT group was significantly decreased after TCDD-exposure. However, body weight of crude saponin groups increased throughout the experimental period, although the increasing rate was slower than that of NC group. Decrease in body weight was not observed during the experimental period in RGE-CS 40. Increases in triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), AST, ALT and $Fe^{2+}$ levels by TCDD intoxication were significantly attenuated by the RGE-CS treatment. Decrease in glucose, amylase, lactate dehydrogenase (LDH) and creatinine kinase (CK) by TCDD also were inhibited by the RGE-CS. These results suggest that saponin from red-ginseng efflux might be a useful protective agent against TCDD, an endocrine disrupter.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.33-41
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• 2009

Among the toxicants in the environment dioxin-like compounds, including TCDD(2,3,7,8-Tetrachlorodibenzo-p-Dioxin), are well known as carcinogen and teratogen. TCDD the most toxic of these compounds, may result in a wide variety of adverse health effects in humans and environment, including carconogenesis, hepatotoxicity, teratogenesis, and immunotoxicity. Also TCDD increases superoxide, peroxide radicals and induces oxidative stress that leads to breakage of DNA single-strand and mitochondrial dysfunction. Recently, there have been reports that persistent organic pollutants(POPs) may be causing metabolic disease through mitochondrial toxicity. In order to examine if dioxin brings about toxicity on mitochondria directly, we measured the change of the mitochondrial membrane potential after exposure to TCDD using JC-1 dye. After short time exposure of dioxin, mitochondrial depolarization was observed but it recovered to the control level immediately. This TCDD effect on mitochondrial membrane potential was not correlated either to the production of reactive oxygen species(ROS) or extracellular $Ca^{2+}$ by TCDD. Less than 2 hours exposure of TCDD did not show any change in ROS production but 0.25 nM TCDD for 48 hours or 0.5 nM TCDD for 12 hours exposure did increase in ROS production. Under these conditions of ROS production by TCDD, no changes in the mitochondrial membrane potential by TCDD was observed.

• Environmental Mutagens and Carcinogens
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• v.26 no.1
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• pp.1-6
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• 2006

To enhance our understanding of toxicity mediated through the pathway by which TCDD stimulates gene expression, we have investigated genes whose expressions are changed after treatment with TCDD and/or MNNG in human Chang liver cell. First, we treated with MNNG and TCDD for two weeks to transform human Chang liver cell. We obtained cell looks like to be transformed and compared the differential gene expression by using cDNA chip (Macrogen) which carrys genes related with signal transduction pathways, oncogenes and tumor suppressor genes, etc. We found that TCDD up- or down-regulated 203 and 111 genes including oncogenes and tumor suppressor genes in human Chang liver cell two fold or more, respectively. Second, we compared the differential gene expression after treatment with TCDD only by using cDNA chip (Superarray) which carrys genes related with cell cycle regulations, and found that TCDD up regulated genes related with cell proliferation as well as cell growth inhibition in human Chang liver cell two fold or more, respectively. These results suggest that toxicity induced by TCDD may reflect sustained alterations in the expression of many genes and that the changes reflect both direct and indirect effects of TCDD.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.91-98
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• 2004

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) is a powerful carcinogen in several species, limited model system exist to study carcinogenicity of this compound at cellular level. To enhance our under-standing of carcinogenicity of TCDD at cellular level, we investigated micronucleus (MN) frequency as a index of genetic toxicity and whether TCDD can transform the human cells in culture. Normal human cell lines, skin keratinocyte HaCaT, Chang liver and breast MCF10A cells were used. TCDD did not affect the cell viability of the Chang liver, HaCaT and MCF10A cells. The frequency of micronucleus was increased after treatment of TCDD for 24hr in Chang liver and HaCaT cells, but not changed in MCF10A cells. And we observed putative transformed cells in Chang liver cells exposed to 1 $\mu$M TCDD for 2 weeks. The putative transformed cells were also observed in HaCaT cells with subsequent exposure to TCDD (0.1, 1, 10, 100 nM) for 2 weeks after initial exposure to MNNG, but not observed in MCF10A cells. Collectively, these results indicate that the ability of TCDD to induce micronuclei may be involved in cellular transformation of Chang liver and HaCaT cells. Our putative TCDD-transformed cells of Chang liver and HaCaT are expected to provide a clue to the elucidation of TCDD-induced transformation pathway.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.312-318
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• 2002

Dioxin represents a group of halogenated aromatic hydrocarbons of which 2,3,7,8-tetrachlorod-ibenzo-p-dioxin (TCDD) is well known for its extremely toxic properties as well as ubiquitous presence in our environment and ecosystems. In order to better assess the carcinogenic mechanism of dioxin, we should utilize the reliable biomarkers that can precisely and correctly reflect multi-stage carcinogenesis. When MCF10A cells were exposed to TCDD (10 nM), expression of both CYP1A1 and CYP1B1 was induced in a time-related manner. The expression as well as activity of ornithine decarboxylase was transiently induced by TCDD treatment. In contrast, the induction of COX-2 that is implicated in carcinogenesis as well as inflammation, was not induced by TCDD. In another study, gap-junctional intercellular communication (GJIC) was attenuated by TCDD treatment as revealed by the dye-transfer assay. Based on these findings, TCDD has both tumor initiating and promoting potential in human breast epithelial cells in culture. Also, treatment of MCF10A cells with the carcinogen 7,12-dimethylbenz[a]anthracene plus TCDD resulted in malignant cell transformation as revealed by increased anchorage-independent growth of exposed cells. Additional studies may be necessary to assess the effects of TCDD on multi-stage carcinogenesis in vivo.

• Journal of Food Hygiene and Safety
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• v.18 no.2
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• pp.56-60
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• 2003

TCDD, one of the notorious toxic environmental pollutants, damages various organs including liver and is regarded as an endocrine disrupter. To investigate the effects of Houttuynia cordata Thunb (HCT) on the biochemical parameters of function, liver and serum of TCDD-treated rats were used. Seven days after the injection of TCDD (1 $\mu\textrm{g}$/kg), HCT (200 mg/kg) was administered to rats on every other day for four weeks. The lipidperoxide activity was examined by measuring the level of total cholesterol, HDL-cholesterol, LDL-cholesterol, total lipid and triglyceride (TG) in serum, and malondialdehyde (MDA) in liver tissue of rats. Result showed that lipidperoxidation was inhibited In the significant level when 2,3,7,8-TCDD-damaged rats were treated with HCT.

• Toxicological Research
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• v.14 no.4
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• pp.587-594
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• 1998

In order to understand the mechanism if the regulation of CYP 1A1 gene expression and ethoxyresorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in the isolated perfused female rat liver. CYP1A1 mRNA level and EROD activity were measured in rat liver that was isolated and perfused with various chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), 17$\beta$-estradiol (E$_2$), morin. TCDD or 3MC alone perfusion into female rat liver resulted in increase of CYP 1A1 mRNA level and the magnitude of stimulation was six times higher with TCDD treatment than 3MC treatment. However E$_2$ perfusion into female rat liver showed inhibition of CYP 1A1 mRNA level. When 10$^{-8}$ M E$_2$ was administered concomitantly with either 10$^{-9}$ M TCDD or 10$^{-9}$ M 3MC, stimulated CYP 1A1 mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYP 1A1 mRNA level and result was similar to that was observed with estrogen. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was smaller than that of CYP 1A1 mRNA stimulation in response to TCDD or 3MC perfusion. Unlike CYP1A1 mRNA level, stimulation of EROD activity was greater with 3MC than TCDD. Concomitant perfusion either E$_2$ or morin with TCDD or 3MC inhibited 3MC perfusion or TCDD perfusion stimulated EROD activity. These data suggested that TCDD and 3MC might act diffrently in terms of regulation of CYP 1A1 gene expression in rat liver.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.10
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• pp.231-239
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• 2020

The purpose of this study was to evaluate the effects of gobonyangjeonbang (GYB) on the endocrine function and the antioxidant efficacy of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress in rats. In 2017, to evaluate the efficacy of GYB on oxidative stress, 35 male SD rats were divided into five groups and tested. The normal control group was administered saline as a vehicle, while the TCDD-alone group was administered TCDD (2 ㎍/kg per week) intraperitoneally and with physiological saline, and the test group was administered GYB orally by dividing it into three concentrations (75, 150, and 300 mg/kg) for six weeks. Bodyweight decreased significantly after six weeks of TCDD exposure, when compared to rats in the NC group (p<0.001). However, weight loss from TCDD was significantly protected by administration of GYB at 300 mg/kg (p<0.01). The rat liver induced by TCDD showed cytoplasmic vacuole degeneration, and the hepatic sinusoid and weight increased. As a result of measuring MDA and SOD, both items tended to decrease under TCDD administration. On the other hand, there was no change due to GYB administration, and significance was observed in the GYB 300 mg/kg group compared to the NC group in the SOD result (p<0.05). These findings demonstrated that GYB may have a protective effect against TCDD-induced liver toxicity in rats.