• YAKHAK HOEJI
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• v.51 no.1
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• pp.7-12
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• 2007

Hepatic cirrhosis is an important feature of chronic liver disease. Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic disease. The antifibrotic effects on liver cirrhosis by oriental herbs extraction material were examined in bile duct ligated rats. Oriental herbs extraction (0.99 mg/kg rat weight/day) was administrated to cirrohotic rats for 4 weeks. Liver collagen content of bile duct ligated rats was significantly increased. And liver histology showed collagen fiber deposition was increased as well as the normal architecture was lost with large zone of necrosis being observed. Herbs extraction administrated rats showed significantly decreased liver collagen content, accumulation of collagen fiber in histological analysis, and biochemical markers of hepatic diseases. Those results demonstrate the usefulness of herbs extraction materials as an antifibrotic agent for liver cirrhosis.

• 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.

• 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.

• BMB Reports
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• v.53 no.6
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• pp.311-316
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• 2020

Cholestasis is a condition in which the bile duct becomes narrowed or clogged by a variety of factors and bile acid is not released smoothly. Bile acid-induced liver injury is facilitated by necrotic cell death, neutrophil infiltration, and inflammation. Metformin, the first-line treatment for type 2 diabetes, is known to reduce not only blood glucose but also inflammatory responses. In this study, we investigated the effects of metformin on liver injury caused by cholestasis with bile acid-induced hepatocyte injury. Static bile acid-induced liver injury is thought to be related to endoplasmic reticulum (ER) stress, inflammatory response, and chemokine expression. Metformin treatment reduced liver injury caused by bile acid, and it suppressed ER stress, inflammation, chemokine expression, and neutrophil infiltration. Similar results were obtained in mouse primary hepatocytes exposed to bile acid. Hepatocytes treated with tauroursodeoxycholic acid, an ER stress inhibitor, showed inhibition of ER stress, as well as reduced levels of inflammation and cell death. These results suggest that metformin may protect against liver injury by suppressing ER stress and inflammation and reducing chemokine expression.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.108-114
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• 2002

• Toxicological Research
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• v.17 no.3
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• pp.187-194
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• 2001

The oxidative stress causes the cell damage and death and thereby, stimulates membrane lipid peroxidation. In this study, the correlation between the lipid peroxidation product and the parameter of liver fibrosis (cirrhosis) was investigated in cholestasis induced rats. The Sprague-Dawley rats were divided into 3 groups (sham: sham operation, BDL/S-I and BDL/S-II : bile duct ligation/scission) and were observed for 2 or 4 weeks. After observation period, the organs were weighed and the ratio of organ weight/body weight was calculated. Sera and liver tissue were used for the measurement of malondealdehyde (MDA), parameter of clinical biochemistry, total collagen content and the staining. The ratio of organ weight/body weight in BDL/S-I and BDL/S-II was significantly increased compared to sham operated group. Serological parameters (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and Total bilirubin) in BDL/S-I and BDL/S-II group were significantly higher than those in sham operated group. Concentration of MDA in BDL/S-I (261%) and BDL/S-II(790%) was significantly increased compared to MDA in sham operated group. And the content of hydroxyproline (hyp) in BDL/S-I and BDL/S-II group was significantly increased 2~4 times than in sham operated group. The good correlations between hyp in liver tissue and MDA in sera of sham operated group and all operated group were found (r=0.825). The significantly higher value of MDA, hyp and serological parameters in BDL/S-I and BDL/S-II group suggests the stimulation of lipid peroxidation and chronic liver damage. Especially the activation of lipid peroxidation and the stimulation of liver fibrosis was stronger in BDL/S-II group than in BDL/S-I group. The stronger fibrosis, portal-portal septum formation, the more massive bile duct proliferation in portal triads and stroma, and hepatocytes swelling were observed in liver tissue of and BDL/S-II group compared to BDL/S-I group. Conclusively, a good correlation between MDA as a lipid peroxidation marker and hyp as a liver fibrotic parameter could be connected with the process of liver fibrosis. Moreover, cholestasis condition may cause jaundice, activation of lipid peroxidation, and collagen accumulation in liver. Additionally, optimal observation period of bile duct obstruction for the screening of antioxidant and antifibrotic effect in rats would be four weeks.

• Toxicological Research
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• v.34 no.3
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• pp.241-247
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• 2018

Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes ($Col1{\alpha}1$, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.

• Toxicological Research
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• v.12 no.2
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• pp.213-221
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• 1996

In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.

• BMB Reports
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• v.29 no.2
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• pp.142-145
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• 1996

To investigate the cause of increased plasma catecholamine levels in liver disease, catechol-O-methyltransferase (COMT), which provides a major route of catabolism for circulating catecholamines, was studied under the cholestasis induced by mechanical biliary obstruction in rats. Monoamine oxidase (MAO) activity and the $K_m$ and $V_{max}$ values for both enzymes were also measured. Cytosolic, microsomal, and mitochondrial COMT activities in the cholestatic liver were significantly decreased throughout the experiment. Microsomal, and mitochondrial MAO activity in the cholestatic liver were also significantly decreased. Vmax values of COMT and MAO were lower. Serum COMT and MAO activities were detected after CBD ligation. These results indicate that plasma catecholamine levels are increased in liver disease due to decreased hepatic degradation of catecholamines by decreased activities of COMT and MAO. The decreased activity of these enzymes is caused by decreased biosynthesis and by flowage into the blood from the damaged hepatocyte.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.202-202
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• 1994

G009의 hepatic cirrhosis animal model중 bile duct ligation/scission (BDL/S) rat에서의 항섬유화 효과를 조사하였다. BDL/S 수술 후 4주간 투약군에는 G009 saline soln.(5mg/rat/day)을, 대조군에는 saline을 경구투여하였다. fibrosis가 최고에 달하는 4주후 rat를 도살하여, 혈청중 N-terminal procollagen type III peptide(PIIINP) level, 간 조직중 hydroxy proline content, serum biochemical value(ALT, AST, choleterol, total bilirubin, creatinine) 측정 및 간조직검사를 실시하였다. 그 결과 1) 혈청중 PIIINP의 경우, 투약군 BDL/S group(10.3ng/ml$\pm$2.2)이 대조군 (20.5ng/m1$\pm$3.9)에 비해 약 50%정도 유의성 있게 감소하였다(p<0,01). 2) 간 조직중 hydroxy proline치 측정 결과, 투약군 BDL/S group(471$\pm$160$\mu\textrm{g}$/g liver)이 대조군(566$\pm$42.9$\mu\textrm{g}$/g liver)에 비하여 약 13%정도 유의성있게 감소하였다(p<0.05). 3) 간조직검사 결과 투약군의 BDL/S op. group이 대조군보다 necrosis, inflammetion, bile duct proliferation, connective tissue 침착 등이 약화되었다. 위 실험을 종합한 결과 G009는 biliary cirrhosis model에서 antifibrotic effect가 있음이 사료된다.