• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.180.1-180.1
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• 2003

Proanthocyanidins, one of the major natural polyphenolic compounds of grape has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the hepatoprotective effect of proanthocyanidins on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of proanthocyanidins (20, 50mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase, and bilirubin levels. (omitted)

• 분석과학
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• 제7권2호
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• pp.165-171
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• 1994

화학 발암제인 dimetylnitrosamine(DMN)을 Hamster에 구강투여하였을 때 간의 아미노산 조성에 미치는 영향을 규명하기 위하여 reversed phase liquid chromatography법으로 아미노산을 정량하였다. DMN을 투여한 실험군의 간에서의 아미노산의 농도는 대조군에 비해 aspartic acid, glycine, glutamine, histidine, proline, tyrosine, leucine 등은 약 2배, valine, tryptophan은 약 3배, phenylalanine은 약 10배 증가하였고, threonine은 23%로 감소하였으며, serine, alanine, arginine, methionine, isoleucine, lysine은 큰 변화가 없었다.

• Parasites, Hosts and Diseases
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• 제46권3호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.122.1-122.1
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• 2003

Morin, one of the major natural flavonoids has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the hepatoprotective effect of morin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of morin (10, 20mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phospatase, and bilirubin levels. Morin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.116.2-116.2
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• 2003

Aspirin and aspirin-like nonsteroidal antiinflammatory drug have been the mainstay of therapy for rheumatoid arthritis. In this study, we investigated the hepatoprotective effect of aspirin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of aspirin (7.5, 15mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase, and bilirubin levels. Aspirin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.289.1-289.1
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• 2002

Quercetin, one of the most abundant flavonoids in human diet has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of quercetin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral administration of quercetin (10 mg/kg daily for 4 weeks) remarkably prevented this DMN-induced loss in body and liver weight and inhibited the elevation of serum alanine transaminase. aspartate transaminase, and bilirubin levels. (omitted)

• 대한핵의학회지
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• 제37권6호
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• pp.418-427
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• 2003

목적: $^{99m}-lactosylated$ serum albumin ($^{99m}Tc-LSA$)은 간세포에 특이적으로 결합하는 간수용체 영상용 방사성의약품으로 새로이 합성되었다. 간섬유화를 유발하는 dimethylnitrosamine (DMN)을 투여한 간 손상 흰쥐 모델에서 $^{99m}Tc-LSA$의 역동학적인 간섭취를 조사하고 간효소치의 변화와 조직학적 소견을 비교하여, LSA의 간섭취가 간기능의 변화를 반영하는지를 연구하였다. 대상 및 방법: SD계 흰쥐에 DMN를 27 mg/kg으로 복강 내 주사하여 급성 간손상을 유도하고 대조군과 비교하였다. DMN을 주사한 흰쥐를 3일(DMN-3), 8일(DMN-8), 21일(DMN-21)에 $^{99m}Tc-LSA$ (1,665 mg/kg) 29 MBq를 정맥 주사하여, 30분 동안 동적 영상을 획득하고 간과 심장부위에 관심영역을 설정하여 간과 심장부위의 시간방사능 곡선을 얻었다. 간기능 평가를 위해 시간방사능 곡선을 이용하여 간섭취지수와 혈중제거지수를 구하였고 곡선 최적화를 시행하였다. DMN 투여군과 대조군의 간효소치의 변화와 간조직의 광학현미경 소견을 비교하였다. 결과: 대조군에서는 $^{99m}Tc-LSA$가 빠르게 간에 섭취되고 혈중에서 제거되었으나 DMN을 처리한 군에서는 간섭취가 낮았다. 간섭취지수의 비교에서 대조군에 비해 DMN 처리군에서 유의하게 간섭취지수가 낮았다(DMN-3: 0.842, BMN-8: 0.898, DMN-21: 0.91, 대조군: 0.96, p<0.05). 혈중제거지수의 비교에서도 대조군에 비해 DMN 처리군에서 혈중제거지수가 유의하게 높았다(DMN-3: 0.731, DMN-8: 0.654, DMN-21: 0.604, 대조군: 0.473, p<0.05). 비선형 회귀분석에서 $R_2$값은 0.9이상으로 좋은 일치를 보였고, 대조군에서 K값이 DMN처리군에 비해 크고 (DMN-3: 0.28, DMN-8: 0.41, DMN-21: 0.46, 대조군: 0.97, p<0.05), $T_{1/2}$값은 작았다(DMN-3: 2.5, DMN-8: 1.7, DMN-21: 1.5, 대조군: 0.7, p<0.05). 간효소치의 변화는 DMN-3군에서는 대조군에 비해 상승하였으나 DMN-8, DMN-21군에서는 간효소치의 상승이 관찰되지 않았다. 간조직 소견의 경우 DMN-3군에서 중심정맥 주위에 괴사가 관찰되었으나 DMN-8군, DMN-21군에서는 미약한 정도의 염증세포 침윤만이 관찰되었다. 결론: $^{99m}Tc-LSA$ 간신티그래피의 간섭취 정도는 간손상과 반비례하였으며 간섭취의 변화는 조직학적 손상이 심한 정도와 간손상후 회복되는 과정을 반영하여 주었다. $^{99m}Tc-LSA$ 간신티그래피가 간손상을 평가하고 간손상후 회복되는 과정을 추적하는 간수용체 영상용 방사성 의약품으로 사용될 수 있을 것으로 생각된다.

• 생약학회지
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• 제28권4호
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• pp.215-224
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• 1997

Gamijiyu-tang (GJT) described originally in the Dong Eui Bo Gam, a traditional reference for oriental medicine in the Korea, has been clinically used for treatment of chronic liver disease. In order to evaluate scientifcally a hepatoprotective effect of GJT in the liver fibrotic disease, the present study investigated how GJT improves a hepatic function in the dimethylnitrosamine (DMN)-treated rat. DMN treatment caused a significant increase of relative liver weight to the body at 28 days after DMN induction. Administration of with a clinical dose decreased significantly the sAST level $(158.8{\pm}7.76\;IU/L)$ elevated by DMN in jection (p<0.01). A similar phenomenon was also observed at change of both Salt and Salt level in the GJT and/or DMN-treated animal (p<0.01, p<0.05, respectively). A remarkable increase of hydroxyproline was observed by treatment of DMN with comparing to the normal rat $(361.9{\pm}7.35\;vs.\;1278.1{\pm}52.9\;{\mu}g/g\;tissue,\;p<0.01)$. This was significantly reduced by a simultaneous treatment of GJT with DMN for 21 days (p<0.05), but not recovered completely to its normal value. In addition. GJT administration ameliorated conspicuously the DMN-induces histopathological changes of liver such as hemorrhage. Cell necrosis and fibrosis. Tak'en together, results described here demonstrated scientifically in first the medicinal efficacy of GJT by using in vivo animal model, indicating that GJT improves the DMN-induced hepatic injury through reducing an excessive accumulation of collagen and histopathological changes. The decreased collagen content may be a pivotal process for GJT to improve hepatic function in the DMN-induced liver fibrosis. The present study suggests that GJT may be useful for and applicable to the treatment of hepatic fibrosis in chronic liver disease.

• Nutrition Research and Practice
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• 제4권5호
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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.

• 약학회지
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• 제41권5호
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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.