• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.413-418
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• 2004

Objectives : Cirsii Japonici Herba (CJH) is one of medicinal plants that has been frequently used for styptic purposes in Asian countries. In order to evaluate a hepatoprotective effects of CJH in the liver fibrotic diseases, the present study investigated how CJH improves a hepatic function in the dimethylnitrosamine(DMN) treated rat. Methods : CJH were orally administered to rats that has been treated with DMN. Subsequently, the amount of blood L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), and hydroxyproline were quantitated. Several histopathological markers for examining the degree of hepatic fibrosis were investigated by H-E and Masson-Trichrome staining. Results: DMN treatment caused a increase of relative liver weight to the body at 14 days after DMN induction, Administration of CJH with 100mg/kg and 1,000mg/kg dose decreased significantly the AST level elevated by DMN injection(p<0.01). But ALT level was not improved. The hydroxyproline level was reduced by a simultaneous treatment of CJH with DMN for 7 days, but not recovered completely to its normal value, CJH administration improved conspicuously the DMN-induced histopathological changes of liver such as granuloma, but cell necrosis and fibrosis were not improved with CJH 1,000mg/kg dose. Conclusion: These results indicate that CJH has protective effect on liver injury and can inhibit liver fibrosis Induced by DMN in rats.

• Parasites, Hosts and Diseases
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• v.46 no.3
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• pp.127-132
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• 2008

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.84-94
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• 1991

The purpose of this study was to evaluate the influence of high does carbon tetrachloride($CCl_4$) on the hepatotoxic effect of dimethylnitrosamine(DMN) which induces acute hemorrhagic necrosis in liver. Rats were injected intraperitoneally DMN dissolved in physiologic saline by a dose of 40mg/kg. For changes related to $CCl_4$ pretreatment, rats were injected intraperitoneally $CCl_4$ dissolved in olive oil by a dose of 0.4mg/kg, and then injected DMN. The livers were extracted from the rats 3, 6, 12, 24, 48, 72, and 120 hours after $CCl_4$ and/or DMN injection. Liver tissues were examined with light and electron microscopes. The results were summarized as follows ; Light microscopic findings : Severe centrilobular hemorrhagic necrosis developed from 12 hours after injection of DMN and continued to 120 hours. On injection of DMN after $CCl_4$ pretreatment, Massive necrosis occurred early. But active regenerative changes were produced in 24 hours. In 120 hours, the liver recovered in almost normal appearance. The degree of necrosis in pretreated group was similar to that in DMN injection only, and the time of recovery was faster in preteated group. Electron microscopic findings ; The early change was mainly disorganization of RER in DMN injection, and clumping and vesicular dilatation of ER in injection of $CCl_4$. In pretreatment group the early change was similar in appearance with $CCl_4$ group, but severer in degree. According to the results, it was revealed that acute toxic effect of DMN was recovered more rapidly in pretreatment group. Thus it was suggested that $CCl_4$ had protective effect in DMN hepatotoxicity.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.94.2-95
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• 2000

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.139.1-139.1
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• 2001

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.137.2-137.2
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• 2001

• Analytical Science and Technology
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• v.7 no.2
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• pp.165-171
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• 1994

The effect of the chemical carcinogen dimetylnitrosamine(DMN) on the composition of amino acids of the liver in hamsters orally administered with DMN was studied by using the reversed phase high performance liquid chromatography technique. In the liver, the concentration of aspartic acid, glycine, glutamine, histidine, proline, tyrosine and leucine were increased ca. 2-fold of those observed in liver of control group, valine and tryptophan were increased ca. 3-fold, phenylalanine was markedly increased ca. 10-fold, whereas the concentration of threonine was decreased, serine, alanine, arginine, methionine, isoleucine and lysine were unchanged, respectively.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.369-374
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• 2010

Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by ${\alpha}$-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.

• YAKHAK HOEJI
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• v.41 no.5
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• pp.622-628
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• 1997

Hepatic cirrhosis is a common response to chronic liver injury from many causes and is one of the most common cause of all deaths. This study was carried out to compare experimental hepatic cirrhosis in rats to understand this disease and to apply for the pharmacokinetics in disease state. Following three kinds of experimental models were induced; 1) Bile duct ligation/scission (BDL/S), 2) N, N-dimethylnitrosamine(DMN), 3) Carbon tetrachloride. The hepatic cirrhosis was characterized by examing the liver/body weight ratio, serum biochemical values, hydroxyproline content in liver and histopathological lesions in cirrhotic rat liver. The results are as follows : (1) In BDL/S, the liver was enlarged to 250% of normal liver. In contrast the liver was shrinked to 48% and 78% of the normal liver in DMN and carbon tetrachloride, respectively. (2) In carbon tetrachloride and BDL/S, the serum ALT, AST, ALP and total bilirubin levels were significantly increased to 200~300% of normal level, while ALT and total bilirubin levels were significantly increased in DMN group. (3) Hydroxyproline content in cirrhotic rat liver was significantly 200~500% higher than that of normal liver. (4) Nodular formation with fibrosis was observed in BDL/S, DMN, carbon tetrachloride induced cirrhotic rat liver.

• The Journal of Korean Medicine
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• v.18 no.1
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• pp.480-498
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• 1997

This study was to investigate the protective and anticirrhotic effects of Mockhyangjokisan and Haewooljoweetang on the liver cirrhosis or fibrosis induced by prolonged bile duct ligation; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. The development of fibrosis or cirrhosis and its inhibition by the two prescriptions were examined by the chemical analysis of AST, ALT, and hydroxyproline. The results obtained were as follows. 1. The increase of serum asparate aminotransferase induced by bile duct ligation was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 2. The increase of serum alanine aminotransferase induced by bile duct ligation was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 3. The increased level of serum AST and AL T induced by the intraperitoneal injection of dimethylnitrosamine was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 4. The increasing level of hydroxyproline volume in the damaged liver tissues in the rat was decreased by the oral administration of Mockhyangjokisan and Haewooljoweetang extract. But there were no significant differences in the inhibition rate between the two experimental groups.