• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.275-281
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• 2000

Object : This study was carried out to examine the effect of Bupleuri Radix on experimental cholestasis, and make clear apart of this mechanism. Methods : Two models of common bile duct ligation group and taurocholate load group after common bile duct ligation were induced, and Bupleuri Radix extract was taken orally for 14 days. In the 1, 2, 4, 7 and 14 days after treatment, the mitochondrial and microsomal monoamine oxidase(MAO) A and B activities in liver were measured. Results : The mitochondrial MAO A and B activities increased in both Blupleuri Radix treated group after common bile duct ligation and Blupleuri Radix treated group after taurocholate load and common bile duct ligation. MAO A increased in Blupleuri Radix treated group after taurocholate load and common bile duct ligation, and MAO B increased in Blupleuri Radix treated group after common bile duct ligation. The microsomal MAO A activities increased in both Blupleuri Radix treated group after common bile duct ligation and Blupleuri Radix treated group after taurocholate load and common bile duct ligation. Conclusion : According to the result, it is consider that Blupleuri Radix not only improves cholestatis in liver, but also decreases a genetic synthesis of taurocholic acid.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.68-76
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• 2000

Object : This study was earned out to examine the effect of Bupleuri Radix on experimental cholestasis, and make clear a part of this mechanism. Methods : Two models of common bile duct ligation group and taurocholate load group after common bile duct ligation were induced, and Bupleuri Radix extract was taken orally for 14 days. In the 1, 2, 4, 7 and l4days after treatment, cytosolic, mitochondrial and microsomal catechol-O-methyltransferase(COMT) activities in liver were measured. Results : The activities of cytosolic, mitochondrial and microsomal COMT increased in the Blupleuri Radix treated group after common bile duct ligation and after taurocholate load and common bile duct ligation. The activities of cytosolic and mitochondrial COMT increased particularly in Blupleuri Radix treated group after taurocholate load and common bile duct ligation. Conclusions : According to the result, it is considered that Blupleuri Radix not only improves cholestatis in liver, but also decreases a genetic synthesis of taurocholic acid.

• Applied Microscopy
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• v.20 no.1
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• pp.36-50
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• 1990

This experiment was performed to study the morphological responses of the enterochromaffin cells in the duodenal mucosa of rabbit following bile duct ligation. Adult male rabbits were divided into normal, sham operation and experimental groups. Bile duct ligation was performed under ether anesthesia and animals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after operation. Mucosal specimens from the duodenum were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde(0.1M Millonig's phosphate buffer, pH 7.3), followed by postfixation with 1% osmium tetroxide(0.1M Millonig's phosphate buffer, pH 7.3), and embedded within araldite mixture. The sections were cut on a LKB-V ultratome, and observed under a JEM 100CX II electron miroscope. The results were as follow; 1. Irregularities of the nuclei of the enterochromaffin cells were noticed from the 1st day after bile duct ligation, and concentration of the chromatin in the nucleus was more frequently observed on the 7th and the 14th day. 2. The granular endoplasmic reticulum and Golgi complex of the enterochromaffin cell were more developed than those of the normal on the 1st day after bile duct ligation, but they showed poor organization from the 3rd day. 3. Amount of the microfilaments in the enterochromaffin cell was significantly increased from the 5th day after bile duct ligation and they were more frequently observed in the vicinity of the nucleus. 4. Vacuoles with various electron densities in the enterochromaffin cell were increased in number from the 3rd day after bile duct ligation. 5. Glycogen-like particles in the enterochromaffin cell were frequently observed on the 3rd and the 5th day after bile duct ligation. 6. In the early stage of the ligation of bile duct, in the enterochromaffin cells, well developed intracellular organelles, such as granular endoplasmic reticulum and Golgi apparatus were pronounced. But, in the later stage, the cells contained poor organelles, with the some structural sign of necrotic change.

• YAKHAK HOEJI
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• v.42 no.2
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• pp.181-186
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• 1998

This study was attempted to investigate the pharmacokinetics of cyclosporine (10mg/kg, oral) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. The area under the curve (AUC) of blood cyclosporine concentration versus time was significantly increased ($CCI_4$-induced hepatic disorder. Elimination rate constant (Kel) was significantly decreased (p<0.05, p<0.01) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. Volume of distribution (Vdss) and total body clearance (CLtot) were significantly decreased (p<0.01) in rabbits with $CCI_4$-induced hepatic disorder. But Vdss was significantly increased (p4-induced hepatic disorder were 874ng/ml and 2.71 hr, respectively. Cmax and Tmax values in rabbits with bile duct ligation were 105ng/ml and 2.834 hr, respectively. From results of this experiment. It is desirable to do therapeutic drug monitoring of cyclosporine for effective treatment when the cyclosporine is administered to patients with liver disorder m clinical practice.

• Applied Microscopy
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• v.20 no.1
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• pp.51-64
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• 1990

This experiment was performed to study the morphological changes of the goblet cells in the rabbit duodenal mucosa after common bile duct ligation. Healthy adult rabbits weighting about 2kg body weight were divided to normal and bile duct ligated groups. Common bile duct ligation was performed under ether anesthesia. Experimental animals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after the operation. Mucosal specimens from the upper part of duodenum were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde, followed by 1% osmium tetroxide, embedded in araldite mixture, cut with LKB-V ultratome, stained with uranyl acetate - lead citrate, and observed with JEM 100 CX II electron microscope. Observed results were as follow : 1. In the early stages(1st-5th day) of the experiments, the goblet cells showed apocrine and merocrine secretion. But those of the late stage(7th and 14th day) groups showed exocytotic merocrine secretion. 2. In the late stage of the experiments, there found than increase of newly formed goblet cells that contain electron lucent cytoplasms. 3. In the goblet cells of normal rabbit, mucous granules with higher or lower electron densities are found together in the cytoplasm, and electron lucent mucous granules occasionally fused together. But in the early stage of the common bile duct ligation, goblet cells contained granules of higher electron densities. 4. Considering the above findings, common bile duct ligation probably initiates the hypersecretion of mucous granules of goblet cells in the early stage, and may facilitate the differentiation of goblet cells in the later stage.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.193-204
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• 1995

In order to examine the effect of extrahepatic cholestasis induced by common bile duct ligation on the hepatic function, the pharmacokinetics of antipyrine and d-propranolol were investigated in rats. In addition, in an attempt to observe the degree of direct hepatic injury, light and electron microscopic observations and conventional pathologic test using serum were performed. Five days after common bile duct ligation, antipyrine(15 mg/kg) and d-propranolol(3 mg/kg) were intravenously administrated to the rats, respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased. Because hepatic clearance of antipyrine poorly extracted by the liver and that of d-propranolol highly extracted by the liver are respectively dependent on the hepatic intrinsic clearance and the hepatic blood flow, it may be concluded that extrahepatic cholestasis following five days after common bile duct ligation decreased the hepatic intrinsic clearance and the hepatic blood flow. SGPT, SGOT, cholesterol, bilirubin(total bilirubin, direct bilirubin) and alkaline phosphatase were significantly increased(p<0.05). The proliferation of bile ducts was prominent, and degeneration and necrosis of hepatocytes were observed by light microscope. Also, ultrastructurally, bile canaliculi were containing the amorphous materials and losing microvilli, and SER and RER in hepatocytes were dilated and vacuolated.

• Biomedical Science Letters
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• v.10 no.1
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• pp.43-48
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• 2004

Changes of thiol methyltransferase (TMT) activity in cholestatic rat liver were studied. Hepatic subcellular and serum TMT activities were determined in cholestatic rat induced by common bile duct (CBD) ligation over a period 28 days. The mitochondrial and microsomal TMT activities in cholestatic rat liver were found to be significantly increased between the 1st and the 28th day after CBD ligation. The TMT activity in serum was significantly increased throughout the experiments. The Vmax values of the above hepatic TMT in cholestatic rat were significantly increased at the 7th day after CBD ligation. However, the Km values of the above hepatic enzymes did not vary in all the experimental groups. Therefore, the results indicate that the biosynthesis of TMT was increased in cholestatic rat liver. The elevated serum TMT activity is most likely caused by increased hepatocytes membrane permeability due to cholestasis mediated liver cell necrosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.1
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• pp.59-64
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• 1999

Purpose: The aims of this study are to measure the serum levels of fat soluble vitamins (vitamin A and D) from bile duct ligated rats, and to evaluate the effect of oral bile acids administration to facilitate absorption of fat soluble vitamins. Methods: We measured serum ALT, total bilirubin, vitamin A, and vitamin D of Sprague-Dawley rats 1 week before and 4 weeks after experimental bile duct ligation. Rats were consisted with 3 groups. Group 2 had been fed bile acids and group 3 ursodeoxycholic acid after operation for 4 weeks. Multi-vitamin was given to all groups. Results: 1) Base line (mean value before duct ligation): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A $0.87\;{\mu}g/mL$, total bile acids $25.16\;{\mu}mol/L$. 2) Four weeks after ligation: ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A $1.37{\mu}g/mL$, total bile acids $278.22\;{\mu}mol/L$. 3) 4 weeks after ligation, each group (group 1, group 2 and group 3) showed vitamin D (7.62, 8.10 and 7.99) ng/mL, vitamin A (1.68, 1.06 and 1.33) ${\mu}g/mL$, total bile acids (233.17, 345.80 and 268.57) ${\mu}mol/L$, which were statistically not significant. Conclusion: Serum level of vitamin A is increased after bile duct ligation although vitamin D is decreased. Oral administration of bile acids does not affect the serum levels of vitamin A and D in bile duct ligated rats.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.112-118
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• 2001

The effects of Malloti Cortex Water Extract (MCWE), bergenin (isolated as an active component from MCWE), and acetylbergenin (synthesized from acetylation of bergenin) on the liver fibrosis induced by bile duct ligation (BDL) in rats. We studied hydroxypro1ine (HYP) as a marker of collagen accumulation in the liver, alanine aminotransferase (s-ALT), aspartate aminotransferase (s-AST), and alkaline phosphatase (s-ALP) as serum markers of liver cell damage induced by BDL, MCWE, bergenin, and acetylbergenin decreased towards normal the accumulated levels of HYP in the liver and the elevated serum levels of s-ALT, s-AST and 5-ALP. The results indicate that MCWE, bergenin, and acetylbergenin ameliorated the liver damage induced by BDL in rats.

• BMB Reports
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• v.32 no.1
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• pp.67-71
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• 1999

We have investigated the effect of cholestasis on the closely related acyl-CoA:amino acid N-acyltransferase, benzoyltransferase, and phenylacetyltransferase activities in rat liver. Benzoyltransferase and phenylacetyltransferase activities in the liver cytosol, mitochondria, and microsome were investigated for a period of 42 d after common bile duct ligation. Both the mitochondrial and microsomal benzoyltransferases showed significant increase in their activities between the 1st and 7th day after common bile duct ligation, although the cytosolic benzoyltransferase activity did not show a significant change compared to the activities from the sham-operated control. The cytosolic phenylacetyltransferase activity showed a significant increase between the 1st and 2nd day, the mitochondrial activity showed a significant increase between the 2nd and 7th day, and microsomal activity showed a significant increase between the 1st and 7th day, respectively. Enzyme kinetic parameters of hepatic benzoyltransferase were analyzed using benzoyl coenzyme A as a substrate with the preparations from the 1st day post-ligation. Enzyme parameters of hepatic phenylacetyltransferase were also analyzed using phenylacetyl coenzyme A as a substrate with the preparations from the 2nd day post-ligation. The results indicated that although the $K_m$ values of these enzymes were about the same as the sham-operated control, the $V_{max}$ values of both enzymes increased significantly. These results, therefore, suggest that the biosynthesis of benzoyltransferase and phenylacetyltransferase has been induced in response to cholestasis.