• YAKHAK HOEJI
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• v.44 no.5
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• pp.379-383
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• 2000

Stanozolol (STZ, 17$\alpha$-methyl-17$\beta$-hydroxy-5$\alpha$-androstano-(3,2-c) pyrazole), an anabolic steroid, is an abused drug by body-builders or atheletes, as well as medicine for treatment of aplastic anemia and vascular thrombosis. In human volunteers, the major urinary metabolite of STZ was reported to be 3'-hydroxystanozolol that was identified by gas chromatography-mass selective detector (GC/MSD). The objective of this experiment is to investigate the in vitro metabolism of STZ in liver S-9 faction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 faction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100 nmole and the selected time for incubation in the reaction mixture was determined to 60 min. The amount of 3'-hydroxystanozolol produced was increased by about 6-fold in the reaction medium including the liver S-9 fraction of polychlorinated biphenyl-induced rats, compared to that of untreated rats. Inhibitors of cytochrome P450, SKF-525A and 7,8-benzoflavone, decreased the production of 3'-hydroxystanozolol by about 89~100% and 65~75%, respectively; In conclusion, hydroxylation of STZ into 3'-hydroxystanozolol is confirmed by GC/MSD and is catalyzed by cytochrome P450.

• Journal of Sericultural and Entomological Science
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• v.55 no.2
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• pp.40-43
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• 2019

Mature silkworms (MS) of Bombyx mori have enlarged silk glands, which are known to be enriched with various functional materials. A special steaming method has been developed for processing MS with enlarged silk glands edible, by which the MS have become a potential health supplement for improving the quality of life. Steamed and lyophilized MS powder (SMSP) has been strongly believed to have various unidentified beneficial effects for humans. Therefore, the purpose of this mini-review is to summarize the various health promoting functionalities of SMSP, which have been published in the paper so far. Firstly, SMSP increased healthspan as well as lifespan, locomotor ability, and resistance to Parkinson's disease by enhancing olfaction and mitochondrial activity in neurons. Secondly, SMSP increased resistance to carcinogens causing liver cancers, improved both acute and chronic liver function with alcohol metabolism, and prevented alcohol induced stomach ulcers. Thirdly, SMSP reduced UVB-induced skin pigmentations and melanogenesis. Taken together, SMSP can be regarded as a promising natural health product to increase incomes for sericultural farm households in Korea as well as global human health and welfare.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.205-210
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• 2021

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

• Biomedical Science Letters
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• v.28 no.1
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• pp.25-33
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• 2022

The imbalance of oxidative stress due to the excessive production of reactive oxygen species (ROS) leads to the pathogenesis of liver disease. To prevent this, the role of antioxidant mechanisms is important. Antioxidant studies have been reported on the Filipendula glaberrima Nakai. However, studies applied to HepG2 cells, which are human liver cells, have not yet been conducted. In this study, 70% ethanol extract of Filipendula glaberrima Nakai (FGE) was prepared and antioxidant activity was investigated. It was confirmed whether FGE pretreatment could reduce hydrogen peroxide-induced oxidative stress in HepG2 cells. The increase in gene expression of antioxidant biomarkers and the scavenging ability of ROS were measured, and Hoechst 33342 staining was used to know the inhibitory effect of the apoptosis. As a result, FGE significantly increased SOD (2.6-fold), CAT (4.4-fold), MT-1A (3.1-fold), GPx (4-fold), and G6PD (2.4)-fold compared to the H₂O₂-treated group. FGE directly inhibited ROS production from 13.4 to 3.6 (the fluorescence mean of DCF-DA) and also reduced apoptotic cells from 45% to 10% (Hoechst 33342 staining) at 2.5 ㎍/mL. These results demonstrate the excellent antioxidant activity of FGE and show that it can be used as a functional food to prevent liver disease.

• Parasites, Hosts and Diseases
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• v.61 no.2
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• pp.194-197
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• 2023

Ascaris lumbricoides causes one of the most common soil-transmitted helminthiases globally. The worms mostly infect the human small intestine and elicit negligible or nonspecific symptoms, but there are reports of extraintestinal ectopic ascariasis. We describe a rare case of biliary ascariasis mistaken for biliary stent in a 72-year-old female patient with a history of liver resection. She visited our outpatient clinic complaining of right upper quadrant pain and fever for the past week. She had previously undergone left lateral sectionectomy for recurrent biliary and intrahepatic duct stones 2 years ago. Besides mildly elevated gamma-glutamyl transferase levels, her liver function tests were normal. Magnetic resonance cholangiopancreatography revealed a linear filling defect closely resembling an internal stent from the common bile duct to the right intrahepatic bile duct. A live female A. lumbricoides adult worm was removed by endoscopic retrograde cholangiopancreatography (ERCP). Despite a significant decrease of the ascariasis prevalence in Korea, cases of biliary ascariasis are still occasionally reported. In this study, a additional case of biliary ascariasis, which was radiologically misdiagnosed as the biliary stent, was described in a hepatic resection patient by the worm recovery with ERCP in Korea.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.425-433
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• 2023

During liver injury, hepatic stellate cells can differentiate into myofibroblast-like structures, which are more susceptible to proliferation, migration, and extracellular matrix generation, leading to liver fibrosis. Anaerobic glycolysis is associated with activated stellate cells and glyceraldehyde (GA) is an inhibitor of glucose metabolism. Therefore, this study aimed to investigate the anti-fibrotic effects of GA in human stellate LX-2 cells. In this study, we used cell viability, morphological analysis, fluorescence-activated cell sorting (FACS), western blotting, and qRT-PCR techniques to elucidate the molecular mechanism underlying the anti-fibrotic effects of GA in LX-2 cells. The results showed that GA significantly reduced cell density and inhibited cell proliferation and lactate levels in LX-2 cells but not in Hep-G2 cells. We found that GA prominently increased the activation of caspase-3/9 for apoptosis induction, and a pan-caspase inhibitor, Z-VAD-fmk, attenuated the cell death and apoptosis effects of GA, suggesting caspase-dependent cell death. Moreover, GA strongly elevated reactive oxygen species (ROS) production and notably increased the phosphorylation of ERK and JNK. Interestingly, it dramatically reduced α-SMA and collagen type I protein and mRNA expression levels in LX-2 cells. Thus, inhibition of ERK and JNK activation significantly rescued GA-induced cell growth suppression and apoptosis in LX-2 cells. Collectively, the current study provides important information demonstrating the anti-fibrotic effects of GA, a glycolytic metabolite, and demonstrates the therapeutic potency of metabolic factors in liver fibrosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1485-1489
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• 2004

Panax ginseng is the one of best famous phytochemical plant in the world and it's various positive effects such as antioxidant, regulation of immunity are very well known. In this study, we investigated primary the cell viability and morphological change and secondary an antioxidative effect and liver function improvement of extract from Ginseng folium and stem in CCl4 intoxicated rats. The NCTC cell line were used for cell viability and sirius red staining before the animal experiment. The female Sprague-Dawley rats (90-100g) were divided into 3 groups (Normal, AC: CCl₄ treated group, GFS: CCl₄+ extract of Ginseng folium and stem treated group) and acute liver damage was developed by one time administration of CCl₄ mixture (0.5㎖/rat). The liver tissue and sera were collected and used for quantitative measurement of enzyme activity (AST, ALT, ALP, BUN), MDA and Hyp. As a result, cell viability in GFS treated group (in concentration of 3.33-33.33㎎ GFS/200㎕ medium) was 180.9-241.0% significantly and dose dependently higher than in control group. And potential state of cell growth and differentiation and no criteria of cytoplasm lysis and nucleus breaking were observed in control and GFS group. The parameters of liver function (AST and ALP) in sera of GFS group showed significantly 93% and 67.6% lower than AC group (p<0.005-0.05). And the level of ALT and BUN showed fast similar in AC group and GFS group. The concentration of MDA in liver was decreased 576.5% significantly in GFS group when compared with AC group (p<0.005). The content of Hyp in GFS group is merely lower than in AC group. In conclusion, the water extract of Ginseng folium and stem such as Ginseng radix may be possessed the antioxidative effect and improvement of liver function in CCl₄ intoxicated rats.

• Toxicological Research
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• v.21 no.4
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• pp.339-345
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• 2005

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.1
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• pp.48-54
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• 2015

Purpose: Metabolic liver disease (MLD) often progresses to life-threatening conditions. This study intends to describe the outcomes of liver transplantation (LTx) for MLD at a living donor-dominant transplantation center where potentially heterozygous carrier grafts are employed. Methods: We retrospectively evaluated the medical records of 54 patients with MLD who underwent LTx between November 1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative graft and patient survival rates were analyzed according to patient age, and living or deceased donor LTx. Recurrence of the original disease was also investigated. Results: The post-transplant cumulative patient survival rates at one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the patient survival rates according to the recipient age, human leukocyte antigen matching, and living or deceased donor LTx. There were also no differences in the patient survival rates between the MLD and the non-MLD groups for children. Recurrence of the original metabolic disease was not observed in any patient during the follow-up period. Conclusion: Our results suggest that the living donor-dominant transplantation program is well-tolerated in MLD without recurrence of the original MLD using all types of transplantation.

• Journal of Food Hygiene and Safety
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• v.37 no.3
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• pp.198-205
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• 2022

Hepatic diseases are divided into two types: alcoholic and non-alcoholic. Non-alcoholic liver injury finally induces fatty liver and damages liver function. Many studies have demonstrated that Ecklonia stolonifera has antioxidative, anti-inflammatory, and hepatoprotective activities. We conducted a 12-week double-blind, placebo-controlled, randomized trial to examine the efficacy of E. stolonifera extracts (ESE) on biochemical markers of hepatic function. Sixty-five subjects with mild or moderate liver injuries were randomly allocated to receive either 420 mg/d of ESE or a placebo for 12 weeks. Fifty-five participants completed the trial. No significant adverse events were observed among the subjects during the study. The primary end points were changes in plasma levels of aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyltransferase (γ-GT). The secondary end points were changes in lipid profile levels, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Compared with the baseline, AST and ALT levels decreased significantly in the ESE group compared to those in the placebo group (P<0.001). In addition, γ-GT levels in the ESE group were significantly lower than those in the placebo group (P=0.016). There were no differences in the TC, TG, HDL, and LDL levels between groups. In conclusion, ESE consumption for 12 weeks improved liver parameters in subjects with liver injury. Regular consumption of ESE could maintain liver health in individuals at risk of hepatic damage.