• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.305-306
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• 2003

To treat fulminant hepatic failure (FHF) patients, various extracorporeal bioartificial liver (BAL) systems have been developed. Several requirements should be met for the development of BAL systems: hepatocytes should be cultured in a sufficiently high density; their metabolic functions should be of a sufficiently high level and duration; and the BAL systems module should permit scaling-up and aseptic handling. Several investigators have found that freshly isolated primary hepatocytes can be cultured into three dimensional, tightly packed, freely suspended, multicellular aggregates, or spheroids. These specialized cell structures exhibited enhanced liver specific functions and a prolonged differentiated state compared to cells maintained in a monolayer culture. Cells in spheroids appear to mimic the morphology and ultrastructure of the in vivo liver lobule. The ability of hepatocytes to organize into three-dimensional structures was hypothesized to contribute to their enhanced liver-specific activities. In this study, the ammonia removal rate and urea secretion rate of pig hepatocytes spheroids encapsulated in Ca-alginate bead were determined. A packed-bed bioreactor with encapsulated pig hepatocytes was devised as BAL support system. The efficacy of the system was evaluated in vitro.

• The Korean Journal of Pharmacology
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• v.7 no.1
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• pp.37-52
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• 1971

It has been demonstrated repeatedly that the administration of ethionine, a methionine analogue, will produce destruction of pancreatic tissue and liver cells. Destruction of acinar cells of pancreas by the administration of excess methionine similar to that seen after feeding diets supplemented with ethionine was also reported, but the liver was not involved by this amino acid. In an attempt to reproduce the results of these investigators the tissue damages were found to be slight and seen only irregulary in rats receiving ethionine on a complete diet and the result of tissue damages by excess methionine were also controversial. The present studies describe the toxicity of dietary supplemented ethionine and methionine to liver and pancreas in rats fed a low protein diet. Hundred five albino rats weighing around 120 gm were divided into three groups as follows; 1) Control group: A low protein diet containing 8% casein was fed throughout the experimental period. 2) Methionine group: A low protein diet (7% casein) supplemented with 1% methionine was used. 3) Ethionine group: A similar diet as methionine group except the supplementation of 1% ethionine instead of methionine was used. Five animals per wee from each group were killed for 6 weeks. The liver and pancreas were fixed in 10% formalin and histologic sections were prepared and stained with hematoxylin eosin. Serum amylase was expressed as much of glucose liberated from a starch substrate. The glucose was determined by the method of Nelson (1944). Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT) were determined by the technique described in Sigma Bulletin.

• Korean Journal of Veterinary Service
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• v.25 no.4
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• pp.357-370
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• 2002

This experiment was performed to investigate apoptosis during undergoing patho-genesis of Salmonella gallinarum(SG)-infected chicks. 16 days old, 49 chicks was infected with SG (10$\^$6/-10$\^$8/ CFU/㎖) experimentally, they were autopsied to remove liver, spleen, intestine and lung at 1, 6, 12hr, 1, 2, 4 and 7 day post infection(PI) respectively, for H-E and TUNEL staining. Grossly, white foci in the liver and enlarged spleen were seen on 4 day PI and coppery bronze liver, dark-red discolored intestine, green-yellowish discolored and enlarged spleen was observed on 7 day PI. Histopathologically, multi focal necrosis in the liver, follicle hyperplasia in the spleen and inflammatory cells infiltration in the intestine were shown from 2 day PI and more severely observed on 4 day and 7 day PI. In TUNEL analysis, apoptotic cells reached a maximum at 6hr PI in the liver and intestine and at 12hr PI in the spleen, and then decreased the levels of controls by 7 day PI.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.151-163
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• 2011

Objective: The purpose of this study is to observe the effects of Persicae Semen herbal-acupuncture at GB34(Yangneungcheon) on hyperlipidemia of rats caused by high-fat diet. Methods: The author performed several experiments to measure the DPPH radical scavenging activity of PS-HAS,to analyze various components and enzymes in serum and liver, and to observe the histological changes of liver and aorta. Results: 1. Persicae Semen herbal-acupuncture solution increased the DPPH radical scavenging activity in rat's liver cells. 2. In the Persicae Semen herbal-acupuncture group, compared with control group, the level of total cholesterol in serum and the ratio of total cholesterol to HDL-cholesterol decreased significantly. 3. In the Persicae Semen herbal-acupuncture group, compared with the control group, the level of glutathione in liver cells increased significantly. 4. In the Persicae Semen herbal-acupuncture group, compared with the control group, the pathological changes in liver and aorta were reduced. Conclusion: The above results suggest that Persicae Semen herbal-acupuncture at GB34 has good effects on preventing and treating hyperlipidemia.

• Natural Product Sciences
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• v.18 no.2
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• pp.76-82
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• 2012

Stamens of Mesua ferrea L. are a well-known herbal drug used in Indian System of Traditional Medicine to treat various diseases. The claimed activity of this plant part is necessitated to investigate antioxidant and hepatoprotective activity. Authenticated plant sample was extracted with hexane, ethanol (EtOH) and water (aq.) using ASE 100 accelerated solvent extractor. Antioxidant activity was evaluated by means of different in vitro assays. Hepatoprotective effect was investigated on carbon tetrachloride induced oxidative stress in liver slice culture model. Cytotoxic marker lactate dehydrogenase (LDH) released in culture medium and the activity of lipid peroxidation along with antioxidant enzymes (AOEs) namely superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were estimated. Hexane and EtOH extracts were significantly inhibited DPPH, NO, SOD and $ABTS^+$ radical in dose dependent manner. The trade of phenol content was: aq. extract < hexane extract < EtOH extract. A significant correlation was shown by total phenol content and free radical scavenging activity of extracts. The culture system treated with hexane extract, EtOH extract or ascorbic acid exhibited significant depletion in LDH, lipid peroxidation, antioxidative enzymes SOD, CAT and GR. Hexane extract and EtOH extracts of stamen of M. ferrea protected liver slice culture cells by alleviating oxidative stress induced damage to liver cells.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.201-206
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• 2015

The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

• The Journal of Internal Korean Medicine
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• v.26 no.4
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• pp.853-863
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• 2005

Object : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba(ACH) on cultured rat hepatic stellate cells. Methods : Hepatic Stellate Cells were obtained from a 350gm Sprague-Dawley rat by tissue perfusion system, and the cells for the study were selected after 3 passages of culture on non-coated plastic culture dishes which enable the cells to activate, thus producing collagens in the cell media. Cells were treated with various concentrations of Artemisia Capillaris Herba(ACH) extract powder for 24 or 48 hours. After the treatment, Soluble collagen, procollagen levels and the mRNA of the procollagen type I C were measured by using assay kit and RT-PCR method. Results : Procollagen production by the hepatic stellate cells decreased after the treatment in a time-dependent dose-dependent manner. The mRNA expression decreased consistently with the volume of the secreted procollagen which indicates the herb hat inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. Conclusion : These results suggest that ACH is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7785-7792
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• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.177-188
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• 2008

Objectives : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Artemisiae Capillaris Herba extract for 24 hours. The extraction was done either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured by using MTT assay, BrdU assay, RT-PCR, and Procollagen Type I C-peptide EIA Kit. Results : The viability and proliferation of the hepatic stellate cells were decreased as the concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water, which indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However, it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Artemisiae Capillaris Herba, but increased by a high concentration. It seemed that the cells were responding to Artemisiae Capillaris Herba in low- concentrations, thus producing small amounts of collagen. When the drug was administered at high enough concentration to give direct toxicity to cells, the ability of cells to produce collagen was activated, and the overproduction of collagen was observed as an undesirable results. Conclusion : These results suggest that Artemisiae Capillaris Herba is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis when extracted with water in the proper concentrations.

• Applied Microscopy
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• v.23 no.2
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• pp.41-52
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• 1993

This study was designed to observe the ultrastructural characteristics of hepatocytes, endothelial cells, Kupffer cells and Ito cells in the liver of Suncus Murinus. The specimens were processed for electron microscopy, following the immersing in the Karnovsky fixative for 8 hrs and 1% osmium tetroxide for 2 hrs. Hepatocytes contained large number of lipid droplets and large mitochondria. Spaces between the hepatocytes were narrow and in some area were irregular in contours with long and slender microvilli of the hepatocytes. Endothelial cells may contain lysosomes as Kupffer cells do. Bile canaliculi were relatively wide and easily seen in the lobule. Bile ductules located in the space of Disse were formed by the hepatocytes and small cells with or without lipid droplets. The results suggest that the Suncus Murinus liver shows some ultrastructural characteristics of aquatic animal livers, endothelial and Kupffer cells may be the same one only in the different functional states, and the bile ductule may be partly formed by the Ito cell.