• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.178-178
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• 1996

Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.

• BMB Reports
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• v.49 no.3
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• pp.173-178
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• 2016

Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O₂ for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O₂) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O₂, and by decreasing the transcription of CYP7A1.

• Journal of Society of Preventive Korean Medicine
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• v.3 no.2
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• pp.91-100
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• 1999

Today, toxicology is used for many purpose, in many fields. Classification of special toxic effect is related next 4 important principles. 1. The chemical substance must move to target organ or tissue that can induce Biological effect. For this movement, we have to understand the physical-chemical characteristic of substance, and the rout of absorption, metabolism, diffusion and excretion of toxic substance. 2. Every biological effect that induced by chemical substance is not harmful. For example, some specific chemical substance is not harmful in liver enzyme system. 3. The strength of biological effect induced by chemical substance is deep related with dose. Nearly all substance is not effective below the specific dose, and it may toxic to death over the specific dose. It is the 'Dose - response relationship' But carcinogen may toxic whether it is law dose or not. 4. The information that was obtained by experimental animal test, could have to adapt in human biology. Because biological effect of chemical substance could be different in every biological species. In past, drugs was obtained by animal or plants. But in the future, it could be obtained by biochemistry, and genome project. Therefore, in Oriental medicine, research and approach is needed at this time, and have to develop new method of experience in toxic method.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1600-1605
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• 2007

This study was undertaken to investigate the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs. In the experiment, 24 male $Landrance{\times}Yorkshire $weanling pigs were allotted to three groups of 8 animals each. Pigs were fed individually. According to a single factorial arrangement, pigs received diets with 5% of either fresh (group 1 and group 3) or oxidized fish oil (peroxide value was 786.50 meq $O_2/kg$ before inclusion in the diet, group 2). At the beginning of the experiment, pigs in group 3 received an intraperitoneal injection of diquat at 12 mg/kg of body weight. The trial lasted for 26 d. A metabolism test was carried out during the last 4 days of the second week. The results showed that feeding diets containing oxidized fish oil or injection with diquat depressed the growth performance and nutrient digestibilities of weanling pigs, decreased activities of antioxidant enzymes and increased concentration of malondialdehyde in plasma and liver. Intraperitoneal injection of diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet. In conclusion, administration of oxidized fish oil or diquat could induce oxidative stress in weanling pigs, and oxidative stress could depress growth performance and impact anti-oxidative ability of young pigs.

• Nutrition Research and Practice
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• v.1 no.1
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• pp.14-18
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• 2007

This study investigated the effect of physical training and oxidative stress on the anti oxidative activity and on plasma lipid profile. Forty eight rats were given either a physical training or no training for 4 weeks and were then subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). The antioxidative activity was evaluated with the activities of catalase in plasma and superoxide dismutase (SOD), the ratio of reduced glutathione/ oxidized glutathione (GSH/GSSG) and the level of malondialdehyde (MDA) in liver. The plasma concentrations of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C)) were also compared. Compared to those of non-training group. catalase activities of training group were lower before exercise but higher during and after exercise. SOD activities were higher regardless of exercise. GSH/GSSG ratio was higher before exercise but was not significantly different during exercise and even lower after exercise. There were no differences between non-training group and training group in MDA levels regardless of exercise. Compared to those of non-training group, atherosclerotic index of training group was lower after exercise and there were no significant differences before and during exercise. There were no differences between non-training group and training group in HDL-C regardless of exercise. These results suggest that moderate physical training can activate antioxidant defenses and decrease the atherosclerotic index and this beneficial effect is evident under exercise-induced oxidative stress.

• Nutrition Research and Practice
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• v.12 no.5
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• pp.365-370
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• 2018

BACKGROUND/OBJECTIVES Oxidative stress is a major cause of cancer. This study investigated the effects of the ethanol extracts from germinated and non-germinated Keunnunjami rice, a blackish-purple pigmented cultivar with giant embryo, on selected human cancer cell lines and on the antioxidant defense system of mice fed with a high-fat diet. MATERIALS/METHODS: High fat-fed mice were orally administered with either distilled water (HF) or extracts (0.25%, w/w) from brown (B), germinated brown (GB), Keunnunjami (K), and germinated Keunnunjami (GK) rice. RESULTS: In comparison with the brown rice extract, Keunnunjami extract showed higher anticancer effect against cervical and gastric cell lines but lower anticancer activity on liver and colon cancer cells. Mice from the HF group showed significantly higher lipid peroxidation and lower antioxidant enzyme activities than the control group. However, the oxidative stress induced by high-fat diet markedly decreased in B, GB, K, and GK groups as compared with the HF group. CONCLUSIONS: Germination may be an effective method for improving the anticancer and antioxidative properties of Keunnunjami rice and extracts from germinated Keunnunjami rice may serve as a therapeutic agent against cervical and gastric cancers and oxidative damage.

• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.258-266
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• 2015

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMFA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMFA models were generated using different alignments and the best model yielded a cross-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.200-204
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• 2010

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life ($t_{1/2}$) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance ($CL_t$). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.3
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• pp.525-530
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• 1998

The effects of godulbaegi(Ixeris sonchifolia H.) powder on body weight gain, lipid and protein concentrations, and enzyme activities were studied in growing male rats for 4 and 8 week. The fats (Sprague-Dawley) were fed diets containing 5% godulbaegi or without. The body weght gain, food efficiency ratio, protein efficiency ratio, hemoglobin concentration and hematocrit value of rats fed godulbaegi diet were similar to the control diet. The ratio of spleen weight to body weight in godulbaegi group for 8 weeks was greater than in that of control group, but they were similar both feeding groups in liver and kidney. The concentrations of the total lipid and triglyceride in serum were increased in rats fed godulbaegi diet for 4 week than in those fed control diet, but those were decreased in rats fed godulbaegi diet for 8 week than in those fed the control diet. The concentrations of the phospholipid, total cholestrol and HDL-cholestrol in serum were decreased in rats fed godulbaegi diet for 8 week than in those fed control diet. The HDL-cholestrol/total cholestrol ratio and athergenic index were similar to both diet groups. There were no differences in growth, serum total protein, albumin concentrations, aspartate aminotransferase and alanine aminotransferase activities between rats fed godulbaegi diet and those fed the control diet.

• Korean Journal of Clinical Pharmacy
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• v.17 no.1
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• pp.33-37
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• 2007

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of diltiazem (15 mg/kg) after oral administration of diltiazem with or without atorvastatin (0.5, 1.5 and 3.0 mg/kg) in rats. Coadministration of atorvastatin increased significantly (p<0.05, 3.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of diltiazem compared to the control group. The total plasma clearance (CL/F) of diltiazem was decreased significantly (p<0.05, 3.0 mg/kg) compared to the control group. The relative bioavailability (RB%) of diltiazem was increased from 1.14- to 1.49-fold. Coadministration of atorvastatin did not significantly change the elimination rate constant $(K_{el})$, terminal half-life $(T_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa.