• Journal of Life Science
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• v.21 no.12
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• pp.1772-1777
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• 2011

Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

• Applied Biological Chemistry
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• v.40 no.6
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• pp.577-582
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• 1997

Effects of four citrus flavonoids, hesperidin, naringin and their aglycones on phosphatidate phosphohydrolase(PAP, EC 3.1.3.3) activity were examined using isolated rat microsomes as an enzyme source. In addition, these flavonoids were tested to see whether they exert any influence on the proliferation and growth in cultured human hepatocytes HepG2 cells. Flavonoids at concentration up to $10{-4}M$ had no significant effect on the number of cells and cell proliferation by MTT cell growth assay method, whereas aglycone flavonoids, hesperetin and narigenin, at concentration of $10{-3}M$ significantly inhibited cell proliferation. Hesperetin inhibited PAP activity in a dose-dependent manner starting at concentration of $10{-5}M$. Narigenin at concentration of $10{-2}M$ inhibited PAP activity markedly, while the other flavonoids did not show any significant effect. The present study, therefore, demonstrated that aglycone flavonoids exerted portent effects on PAP activity and on cell proliferation.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.330-334
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• 2005

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 $\mu$mol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance ($CL_b$) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane ($CL_{exc}$) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent V$_{max}$ and $CL_{linear}$, but the $K_m$ for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

• Toxicological Research
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• v.25 no.1
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• pp.29-33
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• 2009

Phellinus gilvus (PG) is a widely used mushroom for health promotion. We studied the hepatoprotective effect of the polysaccharide aqueous extract of PG (PGP) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Sprague Dawley rats were divided into 5 groups: Normal control, $CCl_4$ control, PGP 50, 100, and 200 mg/kg + $CCl_4$. The levels of serum biochemical parameters, liver lipid peroxide and antioxidant enzymes, and histological appearances were evaluated. The $CCl_4$-induced increments of alanine aminotransferase, asparate aminotransferase, and alkaline phosphatase levels in serum were significantly decreased by PGP-pretreatments. The PGP dose-dependently decreased hepatic malondialdehyde formations in $CCl_4$-treatment groups. Hepatic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were elevated by PGP in $CCl_4$-treatment groups. Histopathological evaluation of liver showed that the loss of hepatocytes, fatty changes, swelling and extensive necrosis of hepatocytes in centrilobular regions of the $CCl_4$-treated rats were ameliorated by PGP pretreatment. The PGP has hepatoprotective and antioxidative effects in $CCl_4$-induced liver injury of rat.

• Molecules and Cells
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• v.45 no.4
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• pp.180-192
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• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

• Biomolecules & Therapeutics
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• v.13 no.4
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• pp.232-239
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• 2005

An aqueous extract of oriental herbal composition named Onchengyeum and curcumin, an antioxidant isolated from turmeric (Curcuma Zonga L.) reduced hepatotoxicity induced by carbon tetrachloride ($CCI_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE), total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-CHO), high density lipoprotein cholesterol (HDL-CHO), total protein (TP), albumin (ALB) and total bilirubin (BIL) in serum. Hepatic parameters monitored were levels of cholesterol (CHO), triglyceride (TG), and malondialdehyde (MDA) and activities of cytochrome P450 (CYP), NADPH-CYP reductase, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The histopathological examination showed that the treatment of Onchengyeum and curcumin relieved the ballooning degeneration of hepatocytes which had been generated by $CCI_4$. The results suggested that hepatoprotective effects of Onchengyeum and curcumin possibly are due to their promising antioxidative activity.

• Korean Journal of Pharmacognosy
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• v.27 no.2
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• pp.111-116
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• 1996

The components were isolated from the root of Astragalus membranaceus and their structures were characterized as 3,4-methylenedioxypyrrolealdehyde, $7-O-{\beta}-D-glucopyranosyl$ 7, 3'-dihydroxy-4'-methoxy isoflavone and a naphthalene derivative on the basis of spectral and physical methods. $7-O-{\beta}-D-glucopyranosyl$ 7, 3'-dihydroxy-4'-methoxy isoflavone and the naphthalene compound showed protective effect on $CC_{l4}-induced$ cytotoxicity in primary cultured rat hepatocytes.

• Korean Journal of Veterinary Pathology
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• v.5 no.2
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• pp.43-48
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• 2001

Ducklings collected from three farms, having history of rapid onset and spread of nerve signs including kick spasmodically with legs and opisthotonos, were pathologically, barteriologically, virologically examined. Grossly, multiple petechial to ecchymotic hemorrhages were detected in the swollen liver. Histopathologically, diffuse coagulative necrosis of hepatocytes was characteristic in acute cases. Chronic cases revealed marked bile duct hyperplasia rather than hepatocyte necrosis. Some of these cases exhibited multiple granulomas consisting of macrophages, heterophil, fibrin and necrotic cell debri. Filtered homogenate of livers sampled from ducklings caused embryo death with marked hemorrhage and swollen of liver after inoculation into chorioallantoic membrane. Three strains of Salmonella app.,S montevideo, S hadar, and S give, which were biochemically and serologically identified, weir isolated from ducklings of three farms, respectively. From these results, these ducklings were concurrently infected with duck hepatitis virus and Salmonella spp.

• Korean Journal of Veterinary Research
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• v.14 no.2
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• pp.215-219
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• 1974

Ngaione isolated from leaves of Myoporum deserti was dosed to the phenbarbitone and SKF 525 A pretreated male rat and studied the liver lesions. The results obtained were summarized as follows: 1. The liver lesions are mostly zonally distributed and involved the midzonal parenchyma chiefly with tendence to include also associated periportal hepatocytes. 2. The histopathology of liver due to ngaione after phenoharbitone pretreatment is characterized by the consistent pretence of degeneration and necrosis of the periportal parenchyma. 3. Zonal liver lesions caused by ngaione in the SKF 525 A pretreated rat are consistently periacinar in location.

• Archives of Pharmacal Research
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• v.23 no.3
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• pp.237-239
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• 2000

The antioxidant activity of Artemisia montana was determined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and inhibitory activity against free radical generation of hepatocytes ($AC_2$F). The methanol extract of A. montana showed strong radical scavenging activity at a concentration of $10.1{\mu}g/m{\ell}$, and thus fractionated by solvent extraction. Esculetin and luteolin 7-O-rutinoside (scolymoside) were isolated as the active principles from the EtOAc and interphase fractions, respectively. The antioxidant activity of these compounds were comparable to that of L-ascorbic acid.