• Development and Reproduction
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• v.27 no.2
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• pp.77-89
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• 2023

Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins. It also stimulated apoptosis but reduced autophagic responses. These metformin-induced changes were clearly reversed by compound C, an inhibitor of AMP-activated protein kinase (AMPK). Interestingly, metformin massively increased the production of reactive oxygen species (ROS), which was completely blocked by compound C. Metformin also stimulated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Finally, inhibition of p38MAPK mimicked the effects of compound C, and suppressed the metformin-induced fat accumulation and apoptosis. Taken together, metformin stimulates dysregulated glucose metabolism, intracellular fat accumulation, and apoptosis. Our findings suggest that metformin induces excessive glucose-induced DNL, oxidative stress by ROS generation, activation of AMPK and p38MAPK, suppression of autophagy, and ultimately apoptosis.

• Herbal Formula Science
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• v.16 no.1
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.226-234
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• 2006

Disturbance of antioxidant system is very common in chronic alcoholics and herbal or natural products with antioxidant activity have been used for its treatment. This study was to investigate the effect of Vitis vinifera extract(V), Schisandra chinensis extract(S), Taraxacum officinale extract(T), Gardenia jasminoides extract(G), Angelica acutiloba extract(A) and Paeonia japonica extract(P), and their combinations on the antioxidant and ethanol oxidation system. Male Sprague-Dawley rats were subjected to Lieber-DeCarli ethanol liquid diet(ED) and were then given different herbal extract mixtures for 6 weeks including VST(V 100+S 150+T 150mg/kg/day), VSG(V 100+S 150+G 150mg/kg/day), VTG(V 100+T 150+G 150mg/kg/day), and VAP(V 100+A 150+P 150mg/kg/day). When the activity of alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) were compared between ED only group and herbal extracts treatment group, the differences were statistically significant. Phase I and II(glutathione-S-transferase, phenol sulfatransferase) enzyme activities were found to be significantly higher in the VAT treatment group compared to the ED group. Herbal extracts not only repressed the ethanol-induced elevation of malondialdehyde level, but also protected against ethanol-induced decrease in glutathione content, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. The administration of the herbal extracts was found to be effective in eliminating lipid-peroxides induced by long-term consumption of alcohol by activating various enzyme systems and physiological active compound formation system. After a chronic consumption of alcohol, Angelica Radix protected the liver via activating the ethanol-metabolism enzyme system, and Paeoniae Radix via activating the ethanol-metabolism enzyme and the phase I, II-metabolism enzyme system. Taraxaci Herba was also effective in liver protection via activating the ethanol-metabolism enzyme system and the phase I, II-metabolism enzyme system, Gardeniae Fructus via activating the phase II-metabolism enzyme system and the anti-oxidation system enzyme, and Schisandra Fructus and a grapestone via activating the anti-oxidation system. Our data suggest that these herbal extracts may be useful as a health functional food or new drug candidate for fatty liver and hepatotoxicity induced by chronic alcohol consumption.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.52 no.5
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• pp.452-460
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• 2019

Exposure to heavy metals through the consumption of contaminated seafood poses a health risk to humans. In Korea, seafood imports are increasing with consumption, with the largest increase in imported seafood coming from Russia. Peter the Great Bay and the Razdolnaya River are both major fisheries and protected areas under the Northwest Pacific Action Plan located near Vladivostok, Russia. This study analyzed heavy metal [cadmium (Cd), lead (Pb), total mercury (tHg), and total (tAs), and inorganic (iAs) arsenic] concentrations in shellfish and crustaceans collected from these areas. Except for iAs, the major toxic heavy metal concentrations of the samples met the national standards (Cd, 0.024-0.982 and 0.003-0.379 mg/kg; Pb, 0.021-1.533 and 0.002 mg/kg; tHg, 0.006-0.015 and 0.036-0.097 mg/kg). The tAs concentrations of three samples exceeded the Russian standard (5 mg/kg, wet weight), whereas the iAs concentrations were extremely low (ND-0.033 mg/kg). Compared with the provisional tolerable weekly intake (PTWI) of the Ministry of Food and Drug Safety and Joint FAO/WHO Expert Committee on Food Additives, the percentages of PTWI of Cd, Pb, and tHg were 0.239%, 0.001-0.049%, and 0.013-0.302%, respectively. These findings reveal that there is no potential health risk by heavy metals through the consumption of Russian seafood obtained in the surveyed areas.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.1
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• pp.1-25
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• 1996

The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.143-153
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• 2009

Objectives The purpose of this study is to get the basic information from patients how much they understood about their medication and also to know whether patients are making reasonable drug choice between Health Functional Foods and Herbal medicine. Methods 500 questionnaires were handed out to the parents of students in two elementary schools located in OO, Junlabukdo province. 421 questionnaires were completed to be evaluated. Results Among 421 subjects, 53.0% were female, and 47.0% were male. The percentages of the subjects consuming Health Functional Foods and herbal medicine were67.7% and 67.8%, respectively. Among those people who consumed Health Functional Food, 44.1% were using nutritional supplements, red ginseng or ginseng products (26.9%), chlorella products (11.5%), and plum extract products (7.7%). As for the reason to consume Health Functional Foods were varied, but 'in order to be healthy, although currently displaying no illness.'(43.0%) were the most responses among the given choices. On the other hand, the reason for consuming herbal medicine was 'In order to grow taller'(26.1%), 'In order to cure weak physical state frequently displaying common illnesses',(25.9%), and 'In order to cure diseases.'(23.3%). For the questions about effectiveness after consumption,the 69.9% subjects said that it seemed to be effected, and that % was slightly higher than that of subjects with consuming Health Functional Foods(64.4%). For question concerning preferences between Health Functional Foods and herbal medicine, 57.5% chose herbal medicine, and this percentage was higher than that of Health Functional Foods(42.5%).As for the reasons of additional consumption of the Health Functional Foods, subject answered as 'Easy to consume.'(41,6%), which was the most common among the subjects consuming Health Functional Foods. On other hand, the subjects of herbal medicine answered as that herbal medicine is 'more effective'(45.7%), and 'more trustworthy in preventing side-effects.'(40.3%). After consumption of the herbal medication, only 3.9% of the subjects consuming either Health Functional Foods or herbal medicine had side-effects. The most common side-effects were 'dermal reaction' which is normally caused by Health Functional Foods and 'indigestion' problems caused by herbal consumption. Conclusions According to the 421 subjects those involved in study, the percentages of consuming Health Functional Foods(67.7%) and herbal medicine(67.8%) were similar. The most commonly consumed products were a type of Health Functional Foods which were the nutrition-supplying products. Ginseng or red ginseng products were the next commonly used products. Health Functional Foods were commonly consumed for preventing illness and maintaining health rather than any other purpose. In contrary, herbal medicines were more commonly consumed for purposes such as for growth or treating certain type of disease. As a result of consumption, more than half of both subject replied as 'satisfied'. As for the side effects, dermal reaction was the most common problem for those with consuming Health Functional Foods, while indigestion was the most common side effect from the subjects with consuming herbal medicine.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.9
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• pp.1128-1136
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• 2017

Previous studies of the caffeine consumption pattern were limited primarily to beverages containing caffeine. Therefore, this study examined the caffeine consumption patterns and levels in beverages and foods containing caffeine among high school students (n=310) in the Yongin region. The participants included 171 boys (55.2%) and 139 girls (44.8%). The daily mean caffeine intake of the respondents was 41.27 mg (0.651 mg/kg) and 36.47 mg (0.696 mg/kg) in boys and girls, respectively. Among the caffeinated food groups, coffee had the highest caffeine intake group in both boys (18.95 mg) and girls (26.28 mg). Girls consumed large amounts of caffeine in the form of Americano-style coffee (20.04 mg), whereas boys consumed more canned coffee (6.77 mg) than girls (2.43 mg, P<0.01). Carbonated soft drinks were the second most prevalent source of caffeine intake in both groups, even though boys (14.29 mg) consumed larger amounts of caffeine than girls (5.85 mg, P<0.001). Multiple regression analysis investigating the major contributing food group to daily total caffeine intake also showed that the highest standardized coefficient was in coffee regardless of gender (boys 0.492, P<0.001 and girls 0.944, P<0.001), followed by carbonated soft drinks and energy drinks. Approximately 95% of high school students consumed normal levels of caffeine, whereas 3.5% of boys and 5.8% of girls consumed excessive amounts based on the standard limit of Korea Food and Drug Administration (<2.5 mg/kg/d) for adolescents. The daily mean caffeine intake of the excess group was 5.38 mg/kg and 6.96 mg/kg in boys and girls, respectively. Consequently, safe daily caffeine intake needs to be determined throughout continuous national management guidelines and nutritional education.

• Journal of Food Hygiene and Safety
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• v.27 no.2
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• pp.176-181
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• 2012

Persistent accidents related to food safety and expanded international trades have urged the world to be aware of the gravity of the accidents. Accordingly many countries have tried to come up with various laws, regulations, measures, support networks and educational programs for the agenda, particularly focusing on harmonizing food safety technologies among nations and fostering professionals. Also, APEC newly organized Food Safety Cooperation Forum (FSCF) in 2007 to exert multi-dimensional efforts to improve food safety for Asia Pacific nations. Up to now, 35 activities have been promoted since 2007 and additional 20 activities are waiting for their turns for action on the list of APEC project agenda. FSCF has the objective that it helps the stakeholders in food supply chain develop their own competence in that area, thus increase international trade among nations and maintain the globe healthy by applying the highest standards and best practices for the management of food safety ranging from production to consumption. To achieve this strategic objective, APEC subsequently formed Partnership Training Institute Network (PTIN) to build up the multilateral networks of specialists from governmental agencies engaging in food safety management, industries, academia and international organizations in Asia-Pacific region. This attempt made it possible for the world to exchange their scientific and technological information concerning food safety and strengthen related education and training. Today, international cooperation is essential for food safety management. Therefore, we need to participate actively in the activities of APEC FSCF to contribute to improving food safety technologies for the member countries of APEC. We also need to connect the domestic support programs with theirs.