• Title/Summary/Keyword: Experimental liver cirrhosis

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Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development

  • Yujin Jin;Kyung-Sun Heo
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.299-310
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    • 2023
  • Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

The Studies on Search of Antifibrotic Effect by Several Herbs Extract in Rat Liver Tissue (수종(數種)의 한약재(韓藥材) 전탕액(煎湯液)이 동물 간조직내 항섬유효능검색에 관한 실험적 연구)

  • Seo Dong-Jin;Lee Chun-Woo;Kim Hong-Gi;Lee Ki-Nam
    • Journal of Society of Preventive Korean Medicine
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    • v.5 no.1
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    • pp.116-133
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    • 2001
  • Antifibrotic drugs could be delayed or inhibited massive collagen deposition in liver tissue or inhibited collagen synthesis. we investigated antifibrotic effects by several herbs(Schisnadra chinensis, Ganoderma japonicum, Sedum sarmentosum, Alisma canaliculatum, Plantago asiatica) extract with observations of collagen accumulation in liver tissue and collagen synthesis in sera. Rats were used for experimental animal that were devided 3 groups(sham control, BDL/S, BDL/S-ER). Rats were operated for inducing liver fibrosis(cirrhosis) by bile duct obstruction. Several herbs were prepared by water extraction and were applicated p. o. $3ml/day$ during 4 weeks. After observation period, rats were sacrificed and liver tissue and sera were collected. In result, the mortality of rats was 35% in BDL/S group and 20% in BDL/S-ER The color of bile juice in BDL/S-ER was bright yellow and murky yellow in BDL/S group. The significantly lower weight of liver($16.21g{\pm}5.3,\;20.58{\pm}2.4$) and spleen($1.96g{\pm}0.96,\;3.93{\pm}0.21$) were shown in BDL/S-ER than that of BDL/S(p<0.05) group. The value of collagen in liver tissue(25.7%) in BDL/S-ER was observed significantly lower than that of BDL/S group (Tab. 2). AST. ALT, ALP, t-bilirubin, BUN levels were low in BDL/S-ER as compared with those of BDL/S group, but the significance was not proven. The trichrome stained liver tissue in BDL/S-ER group was observed mild bile duct proliferation and fibrosis compared with BDL/S group. In conclusion, natural products inhibited new collagen synthesis and delayed massive collagen deposition in liver tissue, so that they have noticeable antifibrotic effects in experimental liver fibrosis(cirrhosis).

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A Case of Choledochal Cyst Complicated by Liver Cirrhosis on Pathology in a 20-Month-Old-Girl (수술 후 임상증상이 호전된 간경화를 합병한 2세 여아에서의 총수담관낭 1례)

  • Bae, Sun Hwan;Choi, Sung Yun;Lee, Tae Seok;Lee, Ho Jeong
    • Clinical and Experimental Pediatrics
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    • v.48 no.1
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    • pp.104-107
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    • 2005
  • Choledochal cyst is considered to be congenital anomalies of the biliary tract, characterized by varying degrees of cystic dilatation at various segments of the biliary tract. A 20-month-old girl was admitted to Eul-Ji general hospital because of abdominal distension. Physical examination revealed marked splenomegaly and hepatomegaly with nodular surface and hard consistency. Laboratory examination showed elevated transaminase level, alkaline phosphatase level and gamma glutamyltranspeptidase level without evidence of cholestasis. Diagnostic imaging study revealed choledochal cyst with Todani classification type 1. Cholecystectomy and Roux-en-Y choledochojejunostomy was performed, and wedge liver biopsy showed diffuse periportal fibrosis with cirrhotic change and ductular proliferation in the portal area. After operation, hepatosplenomegaly and abnormal laboratory examinations improved rapidly, and in 9 months, the liver and spleen became not palpable. We experienced a case of choledochal cyst complicated by liver cirrhosis on pathology in a 20 month-old girl, and removal of choledochal cyst improved clinical manifestations rapidly.

Effect of Structured Information Provided on Self Care Knowledge, Self Care Performance, and Functional Status of Liver Cirrhosis Patients (구조화된 정보제공이 간경변증 환자의 자가간호 지식과 자가간호 수행, 기능상태에 미치는 영향)

  • Jung, Kyong-Sun;Min, Hye-Sook;Song, Young-Sun
    • The Korean Journal of Rehabilitation Nursing
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    • v.10 no.1
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    • pp.29-36
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    • 2007
  • Purpose: The purpose of this study was to identify the effects of structured information provided on self care knowledge, self care performance, and functional status. Method: The data were collected using self care knowledge and performance assessment tool, and functional status assessment tool from both group hospitalized patients at D hospital in Busan. Results: There was a significant improvement(p=.032) in self care knowledge in experimental group compared to the control group. But there were not improvement in self care performance and functional status in experimental group compared to the control group. But comparing to pretest and posttest in experimental group, There were significant improvement in self care performance (p=.003) and functional status(p=.013). Conclusion: Structured information provided showed increased in the degree of knowledge, self care performance, and functional status. But the effect size of program which had been developed in this study was estimated small, so there is needed to modify this program and to research repeatedly.

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Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet

  • Yin, Hu-Quan;Lee, Byung-Hoon
    • Toxicological Research
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    • v.24 no.2
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    • pp.113-117
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    • 2008
  • Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

Effects of Ikgukwhan and Ikgukbowhawhan on the Production of Collagen and the Regeneration of Liver Cells Damaged by Bile Duct Ligation and Dimethylnitrosamine (익국환과 익국보화환의 실험적(實驗的) 간경변(肝硬變)에 대(對)한 효과(效果))

  • Bae Cheol-Ho;Kim Sung-Hwan;Kim Kang-San;Kang Byung-Ki
    • Herbal Formula Science
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    • v.6 no.1
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    • pp.119-139
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    • 1998
  • This study was to investigate the protective and effects of Ikgukwhan and Ikgukbowhawhan 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 ductligation was inhibited by the administration of Ikgukwhan and Ikgukbowhawn extract. 2. The increase of serum alanine aminotransferase induced by bile duct ligation was inhibited by the administration of Ikgukwhan and Ikgukbowhawhan extract. 3. The increase level of serum AST and ALT induced by the intraperitoneal injection of dimethylnitrosamine was inhibited by the administration of Ikgukwhan and Ikgukbowhawhan extract. 4. The increase level of hydroxyproline volume in the damaged liver tissues in the rat was decreased by the oral administration of Ikgukwhan and Ikgukbowhawhan extract. But there were no significant differences in the inhibition rate between the two experimental groups.

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The Effect of Injinho-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosamine and CCl4 in Rats (인진호탕(茵蔯蒿湯) 추출액이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암(肝癌) 형성과 간경변(肝硬變)에 미치는 영향)

  • Lee, Jong-Bum;Heo, Rae-Kyong;Seung, Kee-Moon;Moon, Goo;Lee, Jong-Deok;Won, Jin-Hee
    • Journal of Pharmacopuncture
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    • v.12 no.3
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    • pp.5-24
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    • 2009
  • Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.

Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease

  • Yang, Hye Ran
    • Clinical and Experimental Pediatrics
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    • v.56 no.2
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    • pp.45-51
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    • 2013
  • Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

Influence of Ganyeumilhobang on Acute and Chronic Liver Injury in Experimental Animal (간염1호방(肝炎1號方)이 실험동물(實驗動物)의 급만성(急慢性) 간손상(肝損傷)에 미치는 영향(影響))

  • Choi, Su-Deock;Kim, Young-Jin;Kim, Kang-San
    • The Journal of Internal Korean Medicine
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    • v.19 no.1
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    • pp.22-38
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    • 1998
  • This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

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