• 생약학회지
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• 제32권2호통권125호
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• pp.121-127
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• 2001

The effect of bear bile on 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-induced hepatotoxicity was investigated in 6-week-old C57BL/6 male mice. Bear bile (100 mg/kg or 500 mg/kg) was administered orally daily for 4 weeks, respectively. From the second week, $10\;{\mu}g/kg$ of TCDD was administered to the bear bile-treated animals orally once a week for 3 weeks (a total of $30\;{\mu}g/kg$). There were no specific clinical findings and significant body weight changes in all groups. Although the livers in TCDD-treated mice appeared a severe hypertrophy and many necrotic foci, and changed to yellow-brown color in gross findings, these lesions were remarkably reduced by bear bile administration. The elevated serum activities of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase due to TCDD were significantly decreased by bear bile treatment (P<0.05). The lipid peroxidation induced by TCDD was significantly prevented by bear bile administration (P<0.05). In histological examinations, there were a moderate necrosis of hepatic cells around central veins, severe cytoplasmic vacuolizations, inflammatory cell infiltrations, and remarkable fatty changes in the liver of TCDD-treated animals. However, the lesions were dose-dependently inhibited by the bear bile treatments. These findings indicate that bear bile may have a protective effect against TCDD-induced hepatotoxicity in mice.

• Natural Product Sciences
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• 제15권1호
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• pp.37-43
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• 2009

Oxidative stress is caused by an imbalance between the production of reactive oxygen and an ability of a biological system, to readily detoxify the reactive intermediates or easily repair the resulting damage. It has been suggested that developmental alloxan-induced liver damage is mediated through increases in oxidative stress. The anti-diabetic effect and antioxidant activity of Phaleria macrocarpa (PM) fractions were investigated in alloxan-induced diabetic rats. After two weeks administration of PM, the liver antioxidant enzyme and hyperglycemic state were evaluated. The results showed that oral administration of PM treatments reduced blood glucose levels in diabetic rats by oral administration (P < 0.05). Serum glutamic-oxaloacetic transaminase (sGOT) and serum glutamic-pyruvate-transaminase (sGPT) were also diminished by PM supplementation. The superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities, and glutathione (GSH) level in the alloxan-induced diabetic rats were significantly decreased (P < 0.05) compared to those in the normal rats but were restored by PM treatments. PM fractions also repressed the level of malondialdehyde (MDA) in the liver. Glutathione reductase (GR), glutathione-S-transferase (GST) and $\gamma$-glutamylcysteine synthase (GCS) were also reduced in alloxan-induced diabetic rats. PM fractions could restore the GR and GST activities, but the GCS activity was not affected in rat livers. From the results of the present study, the diabetic effect of the butanol fraction of PM against alloxan-induced diabetic rats was concluded to be mediated either by preventing the decline of hepatic antioxidant status or due to its indirect radical scavenging capacity.

• 대한미생물학회지
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• 제35권2호
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• pp.117-127
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• 2000

The non-ELR-containing CXC chemokines Mig and IP-10 have been shown to function as chemotactic cytokines for activated T lymphocytes. In this study, we examined the potential involvement of Mig and IP-10 in antimycobacterial response of mice immunized or infected with M. bovis BCG. The accumulation of Mig and IP-10 mRNA in resident peritoneal monocytes ($RPM{\Phi}$) was slightly reduced by stimulation with vBCG, and the degree was greater for 24 hr culture even though IFN-${\gamma}$ was added. Expression of Mig, IP-10, and IFN-${\gamma}$ in 24 hr delayed-type hypersensitivity (DTH) response was stronger in vBCG-immune mice than in the non-immune. The increase of DTH measured by foot-pad thickness appears to be clearly related to the levels of chemokines Mig and IP10 messages and those of IFN-${\gamma}$ and IL-12. Stimulation with vBCG for 2 days decreased or completely dropped the levels of Mig message in non-immune or immune splenocytes, respectively, whereas IP-10 message was slightly decreased in 2 days culture. Moreover, messages for IL-12 (p40) showed similar kinetics for Mig. The levels of Mig and IP-10 mRNA during the course of infection with BCG were not readily changed in lungs, livers, and spleens from BCG-infected mice. Although there was no obvious changes of Mig and IP-10 messages in the target organs during infection process, we found that the infection progressed over the first 3 wk before being contained by the emerging immune response suggested from detectable amount of IFN-${\gamma}$ mRNA around this time. In view of selectivity of chemokines Mig and IP-10 for activated T cells, these data suggest that chemokine Mig and IP-10, especially in collaboration with IL-12 and IFN-${\gamma}$, may playa role as T cell recruiters in immune response against mycobacterial infection.

• 생약학회지
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• 제16권2호
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• pp.81-92
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• 1985

The Polygoni Radix and Cynanchi Radix have been used to potentiate the liver functions in clinic of Oriental Medicine. The water extracts of Polygoni Radix and Cynanchi Radix were administered orally to rats intoxicated with carbon tetrachloride and then this experiment have been performed by observing liver fatty degeneration and activities of enzymes such as cytochrome oxidase (CYO), adenosine triphosphatase (ATP), acid phosphatase (ACP), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP). By oral administration of water extracts of the radices between 1 and 10 days, the following results were obtained. 1. The group given Cynanchi Radix extract showed recovery of the fat liver in 4 days, whereas that given Polygoni Radix extract did the recovery in 8 days. 2. In cytochrome oxidase activity, the group given Cynanchi extract showed normal activity in 6 days, whereas that given Polygoni Radix extract did the activity in 8 days. 3. In adenosine triphosphatase activity, the groups given Cynanchi Radix and Polygoni Radix extracts showed normal activities in 2 and 8 days, respectively. 4. In acid phosphatase activity, the groups given Cynanchi Radix and Polygoni Radix extracts showed recovery of the activities in 2 and 4 days, respectively. 5. In lactate dehydrogenase activity, the group given Cynanchi Radix and Polygoni Radix extracts showed recovery of the activities in 6 and 10 days, respectively. 6. In alkaline phosphatase activity, the group given Cynanchi Radix extract showed normal activity in 2 days, whereas that given Polygoni Radix extract showed slight recovery between 4 and 6 days followed by decrease of the activity in 8 and 10 days. From the above-mentioned results, it was found that both of the water extracts of Polygoni and Cynanchi Radix possessed the recovery action of liver function as intoxicated with carbon tetrachloride in rats. It is also noted that the extract of Cynanchi Radix showed more potent activity than that of Polygoni Radix.

• 한국가금학회:학술대회논문집
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• 한국가금학회 2000년도 제17차 정기총회 및 학술발표
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• pp.36-53
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• 2000

Five experiments were conducted to investigate the effects of antioxidants(Santoquin and Oxiban) using fresh or oxidized fat on the performance of broiler chicks. Day-old broiler chicks (except for Experiment 5 in which 6-d-ol birds were given experimental diets for 10 d) were fed diets containing fresh or oxidized fat (animal-vegetable fat blend in Experiments 1, 4, and 5 and corn oil in Experiments 2 and 3) with or without graded concentrations of Santoquin (0,250, 500 ppm in Experiments 1 and 2 and 0, in Experiment 4 and 400 ppm with 0.1% lipase in Experiment 5) of 2wk. In all experiments, birds fed fresh fat gained more weight, had better feed/gain, together with higher AME$_{n}$ and apparent fat digestibility (Experiments 1 and 2) than birds fed oxidized fat(P<0.05). There was no interaction among fat sources and antioxidants on the performance of chicks in any experiment. In Experiment 3, Santoquin more than 200 ppm resulted in a reduction in weight gain and feed intake(P<0.05). The livers of chicks fed oxidized fat in Experiments 2 and 5 had higher malondialdehyde (MDA) values (P<0.05) Chicks fed oxidized fat with 250 ppm Santoquin in Experiment 2 had lower liver MDA values, although this situation did not occur in Experiments 1, 4, and 5. These results indicate that antioxidant supplements can alleviate most deleterious effects of feeding oxidized fat and that supplementation of Santoquin more than 200 ppm has a negative effect on the performance of broiler chicks.s.

• Toxicological Research
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• 제29권1호
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• pp.7-14
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• 2013

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.191-191
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• 1998

It has been hypothesized that formation of oxygen-derived free radicals may play an important part in ischemically induced tissue injury. In this study, the effects of vitamin C treatment on hepatic reperfusion model were investigated. Livers isolated from 18 hrs fasted rats were subjected to low flow hypoxia (1 $m\ell$/g liver/min, for 45min) followed by reoxygenation (for 30min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (KHBB, pH 7.4) and vitamin C (0.25, 0.5, 1.0 and 2.0 mM) was added to perfusate. 7-Ethoxycoumarin was used as substrate of phase and metbolism. After hypoxia oxygen consumption significantly dropped but vitamin C 0.25, 0.5 and 1.0 mM treatments restored oxygen consumption to the level of control group. LDH and lipid peroxidation were not changed in all experimental groups. Oxidation, phase metabolism, significantly decreased following hypoxia but improved during reoxygenation. Vitamin C 0.25 mM treatment significantly improved the oxidation of 7-ethoxycoumarin during hypoxia and reoxygenation, but the oxidation significantly decreased by vitamin C 2.0 mM treatment. Similarly, sulfate conjugation decreased in hypoxic group, but this decrease was inhibited by vitamin C 0.25, 0.5 and 1.0 mM treatments. Our findings suggest that hypoxia/reoxygenation diminishes hepatic drug metabolizing function, vitamin C at concentration of 0.25-1.0 mM ameliorates but at higher concentration aggravates these hypoxia/reoxygenation-induced changes.

• 한국수의병리학회지
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• 제2권2호
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• pp.73-84
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• 1998

This study was carried out to investigate on the serum chemistry and the DNA ploidy changes in carcinogenesis of the rat liver and kidney. Sixty male Sprague-Dawley rats were divided into two groups. Group I was non-treated control. Group II was given initiators (2,2'-dihydroxy- di-N-propylnitrosamine, 0.1% in drinking water(d.w.) for 1 week and N-ethyl-N-hydroxy-ethylnitrosamine; 0.15% in d.w. for 1 week) and promoters (3'methyl-cholanthrene; 3'MC, l0mg/kg, intraperitoneally(i.p.) twice a week and DL-serine; 0.05% in d.w. for 5 weeks, from 3 to 8 weeks). All examinations were performed at 12 and 20 weeks RBC, HGBCp＜0.05) and PCVCp＜0.01) significantly decreased in Group II at 20 weeks. Activities of ALT, AST(p＜0.05) and GGT(p＜0.01) were significantly increased in Group II at 20 weeks. Flow cytometric analysis showed hepatocyte nuclei from normal livers were predominantly tetraploid(66~67%) and then diploid(28~30%). Most of hepatocyte nuclei from carcinogen-treated rats were diploid (52~68%) and less were tetraploid(28~42%). Neoplastic liver nodules and hepatocellular carcinoma contained almost exclusively diploid nuclei. Renal cell nuclei from normal kidney were predominantly diploid(88~93%), those from carcinogen-treated rats had an abnormal DNA-content peak(aneuploidy, 6-7%), near the tetraploidy area. These results suggest that diploidy may be an effective screening marker of the liver carcinogenesis. Aneuploidy may be an useful marker in assessment of the experimental renal carcinogenesis.

• 한국동물위생학회지
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• 제24권1호
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• pp.83-88
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• 2001

It is impotent to identify the causative agents of abortion in equine for minimizing the loss of breeding costs in equine Industry. Recently, the abortion has often occurred in equine herds and thus the purpose of the study was aimed at the identification of equine herpesvirus-1, one of the frequent pathogens to abortion, using polymerase chain reaction. Six fetuses to be aborted at nine to ten months in pregnancy reared in six herds were used in the study. Two primers in the PCR were made from glycoprotein B gene of EHV-1. The primers specific for EHV-1 amplified 1880 bp of PCR products from DNA extracts from thorax fluids, livers, lungs, and spleens of four in six aborted fetuses. Consequently, PCR could be applied to diagnose the abortion of EHV-1 and also confirmed to play a major role of the viral pathogen associated with equine abortion in Jeju island.

• 대한수의학회지
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• 제32권4호
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• pp.649-661
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• 1992

This study was performed to compare DNA content by flow cytometer (FCM) and glutathione S-transferase placental form (GST-P) positive foci for searching objective and accurated properties of tumor. Sprague-Dawley rats aged six weeks were divided into three groups and group 1 and 2 of rats were given an intraperitoneal injection of diethylnitrosamine at 200mg/kg body weight and group 3 of rats were given saline. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. Group 1 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for six weeks, group 2 and 3 of rats were begun to feed on basal diets. At 4, 6, and 8 weeks after initiation, all groups of rats were killed, livers were extracted for H & E stain, immunohistochemical stain, and DNA ploidy analysis. In quantitative analysis for GST-P positive lesion number and area by using Image Analyzer, group 1 and 2 represented significant difference in comparison with group 3. In ploidy distribution, diploid cells of group 1 and 2 were increased significantly in comparison with those of group 3 at 4, 6, and 8 weeks after initiation, respectively tetraploid cells were reduced. But S-phase cells were not changed significantly. It is concluded that ploidy change by FCM is useful as objective data for early detection in hepatocarcinogenesis. Therefore, methodology and study of DNA content are carried out for more objective and accurate ploidy analysis in liver tumor.