• Biomolecules & Therapeutics
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• 제16권1호
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• pp.34-39
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• 2008

Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. In the present study, we investigated activity changes of sphingomyelin catabolic enzymes, such as sphingomyelinases and ceramidases by using dimethylnitrosamine (DMN)-treated Sprague-Dawley (SD) male rats hepatic fibrosis model as a hepatic fibrosis model. Twenty rats divided into five groups received: (1) saline; (2) DMN for 1 week, (3) DMN for 2 weeks, (4) DMN for 3 weeks, and (5) DMN for 4 weeks by intraperitoneally 10 mg/kg of body weight for three consecutive days a week. Activities of acidic and neutral sphingomyelinases and acidic, neutral and alkaline ceramidases were measured in the liver and kidney from DMN-treated rats. We found increased ceramidase activities from 2-week and/or 3-week DMN treated rat livers compared to control rat liver. Acidic sphingomyelinase and alkaline ceramidase activities were significantly increased in 3-week DMN-treated rat kidneys compared to control rat kidney. Therefore, sphingolipid metabolizing enzymes and sphingolipid metabolites are supposed to be involved in liver fibrosis, although further investigation is necessary to elucidate meanings of sphingolipids during the liver fibrosis

• 약학회지
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• 제35권6호
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• pp.522-529
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• 1991

The purpose of this research is to evaluate effects of chloramphenicol, phenobarbital and progesterone on damage of DNA, RNA and protein which was induced by dimethylnitrosamine. $N,N-Di[^{14}C]$ methyl-nitrosamine (DMN) was used as a damaging agent and levels of DNA, RNA and protein damage in liver, brain and pancreas were compared with a control group. Pretreatment of mice with chloramphenicol increased protein damage in pancreas two times more than the control level. Liver RNA damage was increased up to 5.8 times and brain DNA damage up to 6.95 times by treatment of phenobarbital but brain RNA damage was decreased significantly down to 21% of the control group. The damage of liver RNA was significantly decreased by treatment of progesterone, although liver protein damage, pancreas RNA damage and pancreas protein damage were increased.

• 대한한의학방제학회지
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• 제6권1호
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• pp.119-139
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• 1998

간경변(肝硬變)은 각종(各種) 만성미만성간염(慢性彌滿性肝炎)이나 광범위(廣範圍)한 간장실질(肝臟實質)의 손상(損傷)이 계속적(繼續的)으로 발전(發展)하여 이루어진 결과(結果)이다. 주(主)된 병리적(病理的) 특징(特徵)은 간세포(肝細胞)의 변성(變成), 괴사(壞死) 후(後)에 나타나는 섬유조직(纖維組織)의 증식(增殖), 간세포(肝細胞)의 결절상(結節狀) 재생(再生), 가소엽(假小葉)의 형성(形成) 등(等)으로서, 이들 세가지의 변화(變化)가 뒤섞여 진행(進行) 되는 가운데, 간내(肝內) 혈관망(血管網)이 감소(減少)하거나 혈관망(血管網)에 이상(異狀) 함몰(陷沒)이 발생(發生)하는 것이다. 주(主)된 임상표현(臨床表現)은 간기능감퇴(肝機能減退)와 문맥압(門脈壓) 상승(上升)으로 인(因)한 비종대(脾腫大), 복수(腹水), 복벽정맥(腹壁靜脈)의 노장(怒張), 식도(食道)와 위저정맥(胃底靜脈)의 노장파열(怒張破裂), 간성혼수(肝性昏睡) 등(等)이 나타난다. 한의학(韓醫學)의 범주(範疇)로는 '적취(積聚), 징가, 황달(黃疸), 고창(鼓脹), 협통(脇痛), 단복창(單腹脹), 비괴' 등(等)에 해당(該當)되는 것으로 습열(濕熱)이 구울(久鬱)함에 따라 간(肝), 비(脾)가 손상(損傷)되고 이것이 더욱 오래되어 기체혈어(氣滯血瘀)로 발전(發展)하게 되는 병리변화(病理變化)를 갖는다. 이에 담도결찰(膽道結紮) 및 dimethylnitrosamine의 복강투여(腹腔投與)로 간경화(肝硬化)를 유발(誘發)하고, 울증(鬱證)에 다용하는 익국환과 익국보화환이 이러한 병증(病症)에 간기능보호작용(肝機能保護作用)이 있는가를 관찰(觀察)하고, 한의학적(韓醫學的) 병증(病症)의 분류(分類)에 따라 간질환(肝疾患)에 대(對)한 치료(治療)의 가능성(可能性)을 알아보고자 본(本) 실험(實驗)을 실시(實施)한 결과(結果), 유의성(有意性) 있는 결과(結果)를 얻었기에 보고(報告)하는 바이다.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.243-248
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• 2008

In the present study, we investigated activity change of sphingomyelin anabolic enzymes such as sphingomyelin synthase and ceramide synthase. Sprague-Dawley male rats treated with 10 mg/kg of DMN intraperitoneally were used as a hepatic fibrosis model. Sphingomyelin synthase and ceramide synthase activities were measured in 1-week, 2-week, 3-week and 4-week DMN-treated rats along with respective control group rats. We found the increased sphingomyelin synthase activity in 4-week DMN-treated liver but not in kidney. Ceramide synthase activity was significantly increased in DMN-treated kidney after 2-week treatment and in DMN-treated liver after 3-week treatment. Although further investigation is necessary to elucidate meanings of sphingolipid metabolites during the liver fibrosis, activity change of sphingolipid anabolic enzymes may imply that sphingolipid metabolism and sphingolipid metabolites could be involved in liver fibrosis especially under oxidative stress.

• 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.179.3-180
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• 2003

Solanum lyratum (Solanaceae) has been used as a traditional analgesic, antipyretic and hepatoprotective agents in Korea. In this study, we investigated the hepatoprotective effect of ethylacetate extract of Solanum lyratum (SL) on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of SL (150, 300 mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase levels. (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.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)

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.87-90
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• 2012

Cholangiocarcinoma (CCA) is the most common cancer in northeastern Thailand. At present, effective diagnosis of CCA either in humans or animals is not available. Monitoring the development and progression of CCA in animal models is essential for research and development of new promising chemotherapeutics. Ultrasonography has been widely used for screening of bile duct obstruction in CCA patients. In this study, we preliminarily investigated the applicability of ultrasonography to monitor the development and progression of CCA in Syrian golden hamsters (n=8) induced by Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN) administration. Ultrasonography and histopathological examination of hamsters was performed at week 0, 20, 24 and 28 of OV infection or at the start of water/Tween-80 administration to controls. The ultrasonographic images of liver parenchyma and gallbladders of OV/DMN-induced CCA hamsters showed sediments in gallbladder, thickening of gallbladder wall, and hypoechogenicity of liver parenchyma cells. The ultrasonographic images of liver tissues were found to correlate well with histopathological examination. Although ultrasonography does not directly detect the occurrence of CCA, it reflects the thickening of bile ducts and abnormality of liver tissues. It may be applied as a reliable tool for monitoring the development and progression of CCA in animal models in research and development of new promising chemotherapeutics for CCA.

• Parasites, Hosts and Diseases
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• 제32권1호
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• pp.13-18
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• 1994

간흡충은 담관내에 기생하면서 만성적 감염의 결과 최종적으로 담관암을 유발시키는 것으로 알려져 왔다. 실험동물에서 간흡충의 감염만으로는 담관암이 발생하지 않으며, 어떠한 외적 혹은 내적 발암성의 물질들과 병합하여 담관암이 형성하는 것으로 보고된 바 있다 본 실험은 햄스터에서 간흡충의 감염과 dimethylnitrosamine(DMN)의 병합작용으로 담관암이 발생되었다는 모델을 이용하여 "발암기전의 2단계이론" 상에서 간흡충의 역할을 밝혀보고자 하였다. 총 90마리의 햄스터를 15 마리씩 6군으로 나누었다. $DMN{\;}{\rightarrow}{\;}CS$군의 햄스터에서는 먼저 15 ppm의 DMN을 4주 동안 음수 투여하고, 1주 후에 간흡충을 15마리씩 인공감염시켰다. 그리고 5주 후에 piaziquantel로 간흡충을 치료하였다 $CS{\;}{\rightarrow}{\;}DMN$군에서는 먼저 간홉충을 감염시키고 5주 후에 praziquantel로 치료하였으며 1주 후부터 DMN을 4주동안 투여하였다. DMN + CS군에서는 DMN과 간흠충을 동시에 투여하였으며 4주 후에는 DMN을 제거하였다. DMN군과 CS군은 각각 DMN과 간흡충만을 투여하였고 대조군은 아무것도 투여하지 않았다. 모든 실험동물은 13주 후에 부검하였으며 조직병리학적인 방법으로 간장을 검경하여 진단하였다. 실험결과 담관암은 $DMN{\;}{\rightarrow}{\;}CS$군에서 3마리, DMN + CS군에서 11마리가 발생하였으며 나머지 군들에서는 암이 발생하지 않았다. 본 실험으로 2단계 발암기 전상에서 간흡충은 담관암발생을 촉진하는 효과를 보였음을 알수 있었다.