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

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

• Journal of Yeungnam Medical Science
• /
• v.18 no.1
• /
• pp.51-58
• /
• 2001

Background: Cholestatic hepatitis is failure of bile to reach the duodenum with hepatocellular damage and no demonstable obstruction of the major bile ducts. The prognosis is usually good with recovery in less than 4 weeks after withdrawal of the offending drug. However, a prolonged course lasting over 3 months is possible and, in rare cases, progression to ductopenia with development of a vanishing bile duct syndrome occurs. A differential diagnosis with other causes of Chronic liver disease is needed. Materials and Methods: From January 1991 through January 2000, 14 patients diagnosed as cholestatic hepatitis by liver biopsy were included. The possible causative drug, clinical features, laboratory findings, and progression of cholestatic hepatitis were evaluated. The semiquantitative study of liver lesions was performed by two independent observers. Results: Causes of cholestatic hepatitis are 5 cases of oriental medicine, 3 cases of anti-tuberculosis medication, 1 case of ticlopidine and antibiotics and 4 cases of unknown causes. The clinical features of cholestatic hepatitis were jaundice, itching, urine color change, and general weakness. During 6 to 30 months, LFT of 5 patients showed prolonged elevation. Elevated total cholesterol ${\geq}$250 mg/dL in 6 patients, pheripheral blood eosinophilia in 5 patients, auto-antibody positive in 6 patients were observed respectively. The biopsies showed intralobular bilirubinostasis with a mixed portal inflammatory infiltration. Conclusion: In cholestatic hepatitis, durations of abnormal LFT are variable regardless of causative drugs. If cholestatic hepatitis progresses toward chronic course, viral hepatitis, primary biliary cirrhosis, and autoimmune hepatitis should be differentially diagnosed and sequential liver biopsies are needed.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.6
• /
• pp.565-570
• /
• 1999

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver injury. Due to the detergent-like effect of the hydrophobic bile acids, hepatocellular injury has been attributed to direct membrane damage. However histological findings of cholestatic liver diseases suggest apoptosis can be a mechanism of cell death during cholestatic liver diseases instead of necrosis. To determine the pattern of hepatocellular toxicity induced by bile acid, we incubated primary cultured rat hepatocytes with a hydrophobic bile acid, Glycochenodeoxycholate (GCDC), up to 5 hours. After 5 hours incubation with $400\;{\mu}M$ GCDC, lactate dehydrogenase released significantly. Cell viability, quantitated in propidium iodide stained cells concomitant with fluoresceindiacetate was decreased time- and dose-dependently. Most nuclei with condensed chromatin and shrunk cytoplasm were heavily labelled time- and dose-dependently by a positive TUNEL reaction. These findings suggest that both apoptosis and necrosis are involved in hepatocytes injury caused by GCDC.

• Biomedical Science Letters
• /
• v.10 no.4
• /
• pp.421-427
• /
• 2004

The possible mechanisms of decreased monoamine oxidase (MAO) A and B activities in cholestatic rat liver were studied. Hepatic and serum MAG activities were determined from the experimental rats with common bile duct ligation (CBDL). The Michaelis-Menten constants in these hepatic enzymes were also measured. The activities of mitochondrial MAO A and B, and mircosomal MAO B as well as their Vmax values were found to be decreased significantly in CBDL plus taurocholic acid (TCA) injected group than in the control group, such as CBDL alone groups. However, their Km values in the experimental groups did not vary. Serum MAO activity increased significantly in the CBDL plus TCA injected group than in the control group. The above results suggest that TCA represses biosynthesis of the MAO in the liver. The elevated activity of the serum MAO is believed to be caused by the increment of membrane permeability ofhepatocytes upon TCA mediated liver cell necrosis.

• The Journal of Korean Medicine
• /
• v.17 no.2 s.32
• /
• pp.214-226
• /
• 1996

In an attempt to evaluate the effect of high and low concentration of Injinsaryungsan and high and low concentration of Sosihotang on cholestatic liver injery induced by $ANIT({\alpha}-naphthylisothiocyanate)$, biochemical changes in serum transaminase(GOT, GPT), alkaline phosphate, lactate dehydrogenase, total cholesterol, triglyceride, total-bilirubine were studied and the following results were obtained. 1. High concentration of Injinsaryungsan(2.2g／Kg) inhibited significantly the activity increases of GOT, GPT, ALP, LDH, TC, TG, T-Bilirubine induced by $ANIT({\alpha}-naphthylisothiocyanate)$. 2. Low concentration of Injinsaryungsan(1.1g／Kg) inhibited the activity increases of ALP, LDH, TC, TG with statistical significance, while inhibited the activity increase of GOT ,but with no statistical significance. 3. High concentration of Sosihotang(2.4g／Kg) inhibited the activity increases of LDH, TG, TC with statistical significance while inhibited the activity increases of GOT, GPT, ALP, T-bilirubine with no significance. 4. Low concentration of Sosihotang(1.2g／Kg) inhibited the activity increase of TG, while inhibited the activity increase of ALP, TC with no statistical sig-nificance, but didn't inhibite the activity increases of GOT, GPT, LDH, T-Bil. These results suggest that Injinsaryungsan has more significant effect on the liver injury induced by $ANIT({\alpha}-naphthylisothiocyanate)$ compared with Sosihotang and so can be applicable clinically to virus hepatitis and cholestatic liver injury. Further study will be required to evaluate the effect of Sosibotang on cholangitis and cholecystitis.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.107-114
• /
• 2002

Cholestatic liver injury results from the accumulation of toxic bile salts within the liver. The aim of the present study was to understand the mechanism of bile salts-induced hepatocellular apoptosis in bile duct-ligated (BDL) rats, using Western blot and immunohistochemical analysis.(omitted)

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

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.11 no.sup2
• /
• pp.35-43
• /
• 2008

Jaundice is common in breast-fed infants. Any infant noted to be jaundiced at 2 weeks of age need to be evaluated for cholestasis with measurement of total and direct serum bilirubin. The most common causes of cholestatic jaundice in infants are biliary atresia and neonatal hepatitis. Genetic causes of the neonatal hepatitis syndrome are increasingly recognized and idiopathic neonatal hepatitis is decreasing. Cholestasis should be investigated using a structured protocol. Early detection and timely, accurate diagnosis is important for successful treatment and a favorable prognosis. In particular, a Kasai portoenterostomy for biliary atresia has the best outcome if performed before the infant is 8 weeks of age. The management of cholestasis is mainly supportive, including nutritional support and alleviation of symptoms to improve the quality of life. Specific treatments are available for some causes of neonatal hepatitis syndrome and should be started as soon as possible. For decompensated liver disease, liver transplantation yields a better outcome.

• Biomedical Science Letters
• /
• v.11 no.1
• /
• pp.37-43
• /
• 2005

The possible mechanisms of increased aryl sulfotransferase (AST) isozymes activities in cholestatic rat liver were studied. Hepatic AST-I, II and -III, IV activities were determined from the experimental rats with common bile duct ligation (CBDL). The Michaelis-Menten constants in these hepatic enzymes were also measured. The activities of mitochondrial AST-I, II and -III, IV, and microsomal AST-III, IV as well as their Vmax values were found to be increased significantly in CBDL plus taurocholic acid (TCA) injected group than in the control group, such as CBDL alone groups. However, their Km values in the experimental groups did not vary. The results suggest that TCA stimulates biosynthesis of the AST in the liver.