• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.129-130
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• 1994

The science of toxicology is the understanding of the mechanisms by which exogenous agents produce deleterious effects in biological systems. The actions of chemicals such as drugs are ultimately exerted at the cellular and gene levels. Over the past decade. several in vitro alternative methods such as cultured cells for assessing the toxicity of various xenobiotics have been proposed to reduce the use of animals. In this workshop three advanced methods will be presented. These methods are novel important models for toxicologic studies. Dr. Tabuchis group has establishcd two immortalized gastric surface mucosa cell lines from the pminary cultore of gastric fundic mucosal cells of adult transgenic mice harboring a temperature sensitive simian virus 40 large T-anugen gene. As the immortalized cell lines of various tissues possess unique characteristics to maintain their normal functions for several months, these cell lines are extremely useful for not only toxicity testing but also pharmacological screening in new drug development. Professor Funatsu have studied the formation of spherical multicelluar aggregates of adult rat hepatocytes(spheroid) having tissue like structure. The sphcroid shown thre is a prototype module of an artificial liver support system. Thus, the urea synthesis activity of the artificial liver was maintained at least to days in 100％ rat blood plasma. Dr. Takezawa and his coworkers have developed a novel culture system of multicellular spheroids considered 〃organoids〃 by utilizing a thermo-responsive polymer as a substratum of anchorage dependent cells. His final goal is to reconstitute the organoids of various normal organs, e.g., liver, skin etc. and also abnormal deseased organs such as tumor.

• Toxicological Research
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• v.17
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Environmental Analysis Health and Toxicology
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• v.29
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• pp.1.1-1.7
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• 2014

Objectives The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10) in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. Methods Biochemical estimations of brain lipid peroxidation (LPO), reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetyl cholinesterase (AChE), and histopathological investigations of brain tissue were carried out. Results Oral exposure of aroclor 1254 (5 mg/kg) led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]). This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP) which served as a reference standard. Conclusions Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

• Journal of Nutrition and Health
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• v.32 no.7
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• pp.812-820
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• 1999

The aim of this investigation was to assess the difference of health behaviors, dietary patterns and nutrient intakes between smokers and nonsmoker from 435 free living elderly in Kyunggi province. The study subjects were interviewed to collect general characteristics and health behaviors such as smoking, exercise, alcohol consumption, and food habits by questionnaires and nutrient intakes by a 24-hour recall, and weight, height, waist, hip, and blood pressure were measured. The percentages of smoker were 52.3% in males and 12.1% in females. Current smokers were fond of alcohol, salty or hot food, tended to have meals irregularly and insufficient sleep, and were inactive lifestyle compared to nonsmokers. Smokers consumed fewer servings of vegetables, fruits, and beans and their products. Women who smoked consumed less energy, carbohydrates, and vitamin E than nonsmokers, and their nutrient adequacy ratio of protein, iron, phosphate, niacin, vitamin B1, and vitamin C were significantly lower than nonsmokers. There were no differences of nutrient intakes and nutrient adequacy ratio between smokers and nonsmokers in male subjects. In conclusion, elderly smokers tended to have less healthy life style, food habit, and dietary nutrient intakes which may influence the deleterious effects of smoke components on cancer and coronary heart disease risk, thus health education program should include nutrition education as well as smoking cessation.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.3
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• pp.467-480
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• 1999

Many antinutritional and toxic factors abound in tropical seeds, which are also generally rich in nutrients and therefore more prone to attack from herbivores. Antinutritional and toxic factors are considered to defend seeds against environmental vagaries and thus help to protect them. These factors though good for the plant, cause deleterious effects or are even toxic to animals and man. The conventional seeds cultivated for oil or non-oil purposes, and general aspects of antinutritional factors are not presented here as these have already been discussed widely by many workers. Deficits in conventional protein and energy sources in the tropics have stimulated a quest for alternative feeds both for animals and humans. This article attempts to highlight two new oilseed crops, Jatropha curcas and Moringa oleifera, and in addition deals with some under-utilized seeds with potential as animal feed. Most of these seed plants are adapted to various marginal growing conditions in the tropics and can help to mitigate the prevailing deficit in protein and energy sources. Antinutritional and toxic factors in seed or seed meal, various approaches to detoxify seed meal, and future research and development priorities for their exploitation as animal feeds are presented.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.8
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• pp.1102-1106
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• 2009

The Tibetan Mastiff is one of the most archaic, ferocious and the largest dogs in the world. The Kunming dog is the chief working-dog breed in China. In this study, ten microsatellite loci were used to assess the genetic diversity and evolutionary relationships in six dog breeds, including Tibetan Mastiff, Kunming dog, Belgian Malinois, Labrador Retriever, English Springer Spaniel, and German Shepherd. The highest genetic diversity was exhibited by the Tibetan Mastiff, indicating useful protection and little inbreeding in the modern Tibetan Mastiff. Higher genetic diversity was observed in European breeds, supporting the hypotheses that breeders outcross their pure breed dogs occasionally to avoid deleterious effects in Europe. Evolutionary relationships showed that English Springer Spaniel and Labrador Retriever were clustered together, then with the Tibetan Mastiff, consistent with previous cluster results. German Shepherd and Kunming dog were grouped together, coinciding with the breeding history of Kunming dog. It is the first time that Tibetan Mastiff and Kunming dog have been analyzed with microsatellites.

• Journal of Applied Biological Chemistry
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• v.48 no.1
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• pp.11-15
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• 2005

Salinity of soils in greenhouse has been increased by massive application of fertilizers. Nitrogen fertilizer was most popular, and thus nitrate became the majority of soil salinity. Accumulation of nitrate led to deleterious effects on the growth and development of crops and vegetables. Microbial strains able to utilize nitrate and thus remove excess nitrate from farm land soils were isolated from 15 different soils of greenhouses and plastic film houses. Four strains able to grow in medium containing 50 mM $KNO_3$ were isolated, among which only E0461 showed high capacity of nitrate uptake. Nitrate uptake by E0461 was dependent on culture medium and was increased by addition of tryptone and peptone. Although E0461 was able to grow without tryptone and peptone, growth was slow, and no nitrate uptake was observed. Nitrate appeared to facilitate E0461 growth in the presence of tryptone and peptone. Through kinetic analysis, nitrate uptake was measured at various concentrations of nitrate, and half-life was calculated. Nitrate concentration decreased with increasing incubation period, and plot between half-lives and initial concentrations of nitrate fitted to single exponential function. These results suggest one major factor plays an important role in microbial nitrate uptake.

• Nutritional Sciences
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• v.8 no.2
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• pp.89-96
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• 2005

To determine the deleterious effects of chronic alcohol consumption on bone especially in adolescents or young adults, 8 week-old Sprague Dawley male rats were fed with Lieber-Decarli ethanol liquid diet, containing $36\%$ of energy as ethanol, ad libitum (ethanol group) or isocaloric normal liquid diet (control group) for 7 weeks. Body weight was significantly lower in ethanol group than that in control group after 1 week of feeding to the end. liver weight and the ratio of liver or kidney weight to body weight in ethanol group were significantly increased when compared to those in control group. Ethanol group showed significantly lower serum protein and albumin levels (p<0.05), higher total cholesterol and HDL-cholesterol levels (p<0.05), and AST, ALT and BUN activities than control group, but serum triglyceride, Ca and phosphate levels were not different. Ethanol group had significantly lower tibial trabecular bone area and serum osteocalcin level than control group (p<0.05), but urinary Ca and NTx (cross-linked N-telopeptide of type I collagen) concentrations and serum testosterone and parathyroid hormone levels were not different. In conclusion, chronic alcohol consumption in growing young male rats may result in osteopenia through the reduction of bone formation as well as liver malfunction.

• Proceedings of the Korean Environmental Health Society Conference
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• 2002.04a
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• pp.55-56
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• 2002

Aflatoxin is a secondary fungal metabolite and is a public health hazard because it is a human carcinogenic and has many deleterious effects in men and animals. Rice is one of the better substrates for the fungus which can produce aflatoxins. This study was performed to investigate aflatoxin reduction during the cooking and processing of rice. Aflatoxin was produced by Aspergillus parasiticus ATCC 15517 on well-milled rice(Japonica type) at the level of 13.2 ppb. Cooked rice, rice cakes (baek-sol-gi, plain steamed rice bread), fermented rice (sik-hye, sweet rice beverage), and popped rice were prepared from the aflatoxin-contaminated rice. Aflatoxin content in the samples was determined by high performance liquid chromatography. The total aflatoxin level was decreased to 46.9％ in the cooked rice, 85.6％ in the rice cakes, 11.4％ in the fermented rice, and 7.6％ in the popped rice, respectively (p＜0.05). This reduction brought the level of aflatoxins down to below the Standard and Specification of Korea (10 ppb), except for the rice cakes. These results indicate that washing, steaming, fermentation, and popping of rice was helpful in reducing the aflatoxin level in the rice and the most helpful factors were high temperature & high pressure. More research is needed to understand why the preparation of rice cakes did not reduce the level of aflatoxin as much as the other cooking methods.

• Journal of Plant Biotechnology
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• v.7 no.1
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• pp.1-15
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• 2005

Salinity is one of the major limiting factors for agricultural productivity. In plants, accumulation of osmolytes plays a pivotal role in abiotic stress tolerance. Likewise, exclusion or compartmentation of $Na^+$ ions into vacuoles provides an efficient mechanism to avert deleterious effects of $Na^+$ in the cytosol. Both vacuolar and plasma membrane sodium transporters and $H^+-ATPases$ can provide the necessary ion homeostasis. A variety of crop plants were engineered with respect to the synthesis of osmoprotectants and ion-compartmentation, but there are other cellular pathways involved in the salinity responses that are still not completely explored. Genomics approaches are increasingly used to identify genes and pathway changes involved in salt-tolerance. The new knowledge may be used via guided genetic engineering of multiple genes to create crop plants with significantly increased productivity in saline soils. This review surveys how plants deal with high salt conditions and how salt tolerance can be improved by transgenic approaches.