• Toxicological Research
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• v.13 no.3
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• pp.265-274
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• 1997

Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.

• Microbiology and Biotechnology Letters
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• v.24 no.5
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• pp.624-629
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• 1996

The ethanol extracts from Angelica gigas Nakai and Angelica acutiloba Kitagawa were fractionated to diethyl ether and aqueous partitions. Both partitions had strong antimutagenic effect on the MNNG (N-methyl-N-nitro-N-nitrosoguanidine) by Ames mutagenicity test. Diethyl ether fractions exhibited the greatest antimutagenic effect suppressing the mutagenicity of MNNG with inhibition of 78-80%. The ethanol extracts from both species showed the inhibitory effect on the growth of several human cancer cell lines. Especially, the diethyl ether fraction from ethanol extracts was most effective on human hepatocellular carcinoma cells, inhibiting 90-95% of cell growth. However, the aqueous fractions had least inhibition activity on many cancer cells. There was little cytotoxicity on human normal liver cell by ethanol extracts. Diethyl ether fraction from Angelica gigas Nakai ethanol extract had cytotoxicity less than 20% on human normal liver cells, compared with that from Angelica acutiloba Kitagawa ethanol exract. The adding of 0.5 (g/l) of diethyl ether fractions of Angelica gigas Nakai or Angelica acutiloba Kitagawa increased immune activity by enhacing human B and T cells up to three to four times. It was proven that diethyl ether fraction (0.7 g/1) from Angelica gigas Nakai could control blood pressure by suppressing angiotensin converting enzyme activity up to 98%. From TLC, it was appeared that both of diethyl ether partitions had umbelliferon, known to one of active substances from Angelica gigas Nakai and Angelica acutiloba Kitagawa.

• Journal of Nutrition and Health
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• v.32 no.3
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• pp.221-229
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• 1999

Certain indigestible oligosaccharides may benefit gastrointestinal tract via fermentation and proliferation of desirable bacterial species. The purose of this study was to elucidate the effect of selected oligosaccharides, such as fructooligosaccharides(FOS), soybean oliosaccharides(SOE), and highly concentrated branched oligosaccharides(HiBOS), on fecal micorflora proliferation, lipid concentration, lipid peroxide formation and antioxidant enzymes acitivies in plasma and liver of the rats. Thirty two male Sprague-Dawley rats were randomly assigned to one of four treatments ; 1) control diet(AIN-93G diet); 2) control diet +5% FOS ; 3) control diet + 5% SOE ; 4) control diet + 5% HiBOS. The duration of the study was 4 weeks. Fecal bifidobacteria concentration were significantly higher (p<0.05) in the HiBOS group compared with the control after 4 weeks of dietary treatment. FOS and SOE groups also had higher fecal bifidobacteria levels than control, but statistical significance was not found. The concentration of plasma total lipid was decreased by oligosaccharide consumption, especially in HiBOS group(p<0.05). The concentration of plasma total triglyceride was significantly lower in all of the oligosaccharide containing groups compared with the control(p<0.05). The plasma total cholesterol concentration tended to be lower in the oligosaccharide consuming groups than control. The concentrations of hepatic total lipid, triglyceride and total cholesterol were not affected by consumption of oligosaccharides. Thiobarbituric acid reactive substance(TBARS) concentrations and antioxidant enzyme activities in plasma and liver were not affected much by experimental diets. There results suggest that dietary oligosaccharides may be beneficial for increasing intestinal bifidobacteria and lowering plasma lipid levels.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.175-179
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• 2007

The present study was performed to elucidate the hypocholesterolemic action of chitosan on the diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats (n=24) were fed with chitosan-free diet (Control), diets containing 2% or 5% chitosan for 4 weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Body weight gain and food intake of rats did not differ among the groups. The chitosan treated groups showed significant improvement in the plasma concentration of total cholesterol and LDL-cholesterol compared to the control group (p<0.05). Also, the chitosan treated groups decreased the liver concentration of total lipid and total cholesterol compared to the control group (p<0.05). The activity of hepatic cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, was increased by 123% and 165% for the 2% or 5% chitosan diets, respectively. These findings suggest that enhancement of hepatic CYP7A1 activity may be a mechanism, which can partially account for the hypocholesterolemic effect of dietary chitosan in cholesterol metabolism.

• Toxicological Research
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• v.33 no.3
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• pp.219-224
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• 2017

Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key role in lipid metabolism. Since free radicals contribute to metabolic diseases in the liver, this study investigated the effects of free radicals on the regulation of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT-PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP-1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was significantly reduced by N-acetyl-$\small{L}$-cysteine treatment, indicating that reactive oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated whether the hypoxic environments that cause endogenous ROS production in mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to hypoxia also increased Lipin1 expression. In contrast, pretreatment with antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our results show that ROS activate SREBP-2, which induces Lipin1 expression.

• Toxicological Research
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• v.32 no.1
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• pp.21-33
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• 2016

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

• Journal of Applied Biological Chemistry
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• v.55 no.1
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• pp.1-5
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• 2012

Recently, we reported that Jeju ground water contains vanadium components and exerts antioxidant effects in vitro and in vivo via the scavenging of reactive oxygen species and enhancement of antioxidant enzyme activities. In the present study, the antioxidant actions of Jeju ground water were compared with those of tap water against gamma-ray radiation in mice. C57BL/6 mice were irradiated with gamma-ray at a dose rate of 2 Gy. The mice were then given tap water or Jeju ground water for 90 days. Jeju ground water compared with tap water enhanced the activities and levels of superoxide dismutase, catalase, and glutathione peroxidase in irradiated liver tissues. Jeju ground water also enhanced the levels of intracellular reduced glutathione, which is vital for normal liver function and repair. These results suggest that vanadium-containing Jeju ground water can safeguard against the harmful actions of gamma-ray radiation through the support of hepatic antioxidant processes.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.732-739
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• 2009

Metabolic syndrome has been strongly associated with elevated alanine aminotransferase (ALT), a surrogate of nonalcoholic fatty liver disease. We investigated the relationship between metabolic syndrome and elevated ALT in the general Korean population. The study sample was comprised of 4,781 Korean adults who had participated in the 2005 Korean National Health and Nutrition Examination Survey. Metabolic syndrome was defined by National Cholesterol Education Program for Adult Treatment Panel III. Elevated ALT was defined as an enzyme activity > 40 IU/L for men, and > 31 IU/L for women. ALT was measured by enzymatic methods. Among participants, 425 (8.9%) subjects displayed elevated ALT. The odds ratios (ORs) for elevated ALT increased in subjects with obesity or one of components of metabolic syndrome such as abdominal obesity, high blood pressure, high fasting glucose, high triglyceride, and low HDL cholesterol after adjusting for age and sex. The unadjusted OR for elevated ALT increased according to the number of components of metabolic syndrome (OR = 1.5, 95% CI: 0.96-2.32 for 1 component; OR = 3.0, 95% CI: 1.98-4.61 for 2 components; OR = 6.3, 95% CI: 4.29-9.35 for ${\geq}3$ components; p for trend < 0.0001). This trend did not differ after adjustments for putative risk factors including age, sex, BMI, smoking status, and alcohol intake. Metabolic syndrome is implicated as a strong risk factor of elevated ALT in Korean adults.

• Food Science and Biotechnology
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• v.18 no.5
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• pp.1055-1062
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• 2009

This study was conducted to investigate whether dietary chlorella intake could have an effect on antioxidative capacity in rats oxidatively stressed with cadmium (Cd). Sprague-Dawley rats fed dietary chlorella (0, 5, and 10%) for 4 weeks after induction of oxidative stress by exposing to Cd (200 ppm) for 8 weeks. After the oxidative stress applied, plasma and liver malondialdehyde concentrations and xanthine oxidase activities were decreased in 5% chlorella fed group compared to chlorella free group. Although liver heme oxygenase-1 protein expression was not affected by chlorella, the enzyme activity was improved in 5% chlorella fed group. Erythrocyte superoxide dismutase activity and hepatic metallothionein concentration were increased in 5% chlorella fed group. However, 10% chlorella intake had no effect on the improvement of oxidative stress-related enzymes and proteins. These findings suggest that, after induction of oxidative stress with Cd, 5% chlorella intake might improve antioxidative capacity against oxidative stress.

• Korean Journal of Human Ecology
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• v.1 no.1
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• pp.94-102
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• 1998

This study was undertaken to investigate the effects of mustard leaf diet on the lipid metabolism under chronic alcohol administration. Sprague-Dawley male rats were fed either AIN-76 diet(control), control with ethanol, AIN-76 diet plus 5% mustard leaf(mustard leaf), or mustard leaf with ethanol lot 30 days. On the 21st day, all of the rats were given an oral dose of ethanol and blood-ethanol concentration were monitored for the next 5 hours. Lipid and enzyme determinations in serum and liver were carried out after 30 days. The results obtained were summarized as following: 1) Supplementing 5% of mustard leaf did not recover the body weight loss due to chronic alcohol administration. 2) There were no significant differences in blood ethanol concentrations among the experimental groups. 3) Mustard leaf diet decreased the plasma total cholesterol, triglyceride levels increased due to the chronic alcohol administration, but not HDL-, LDL-cholesterol, and liver lipids. 4) Mustard leaf diet decreased ${\gamma}$ -GTP level increased by chronic alcohol administration. Overall, these data suggest that mustard lear can have a recovery function, which was not via ethanol metabolism on the symptoms of alcohol related diseases.(Korean J Human Ecology 1(1) : 94~102, 1998)