• Title/Summary/Keyword: Human liver

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Rubus coreanus Extract Attenuates Acetaminophen Induced Hepatotoxicity; Involvement of Cytochrome P450 3A4

  • Lee, Young-Ik;Whang, Kyung-Eun;Cho, Jin-Sook;Ahn, Byung-Min;Lee, Sang-Bum;Dong, Mi-Sook;Kim, Tae-Hyun
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.455-460
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    • 2009
  • Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes associated with hepatic biomarkers AST and ALT

  • Kim, Hyo-Young;Cho, Seo-Ae;Yu, Jeong-Mi;Sung, Sam-Sun;Kim, Hee-Bal
    • BMB Reports
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    • v.43 no.8
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    • pp.547-553
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    • 2010
  • Biochemical tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are useful for diagnosing patients with liver disease. In this study, we tested the association between copy number variation and the hepatic biomarkers AST and ALT based on 8,842 samples from population-based cohorts in Korea. We used Affymetrix Genome-Wide Human 5.0 arrays and identified 10,534 CNVs using HelixTree software. Of the CNVs tested using univariate linear regression, 100 CNVs were significant for AST and 16 were significant for ALT (P < 0.05). We identified 39 genes located within the CNV regions. DKK1 and HS3ST3B1 were shown to play roles in heparan sulfate biosynthesis and the Wnt signaling pathway, respectively. NAF1 and NPY1R were associated with glycoprotein processes and neuropeptide Y receptor activity based on GO categories. PTER, SOX14 and TM7SF4 were expressed in liver. DPYS and CTSC were found to be associated with dihydropyrimidinuria and Papillon-Lefevre syndrome phenotypes using OMIM. NPY5R was found to be associated with dyslipidemia using the Genetic Association Database.

A Case of Probable Mixed-Infection with Clonorchis sinensis and Fasciola Sp.: CT and Parasitological Findings

  • Kim, Tae-Yun;Lee, Yun-Sik;Yun, Ji-Hye;Kim, Jeong-Ju;Choi, Won-Hyung;Oh, In-Hwan;Song, Hyun-Ouk;Chu, Jong-Phil
    • Parasites, Hosts and Diseases
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    • v.48 no.2
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    • pp.157-160
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    • 2010
  • We report here a human case probably mixed-infected with Clonorchis sinensis and Fasciola sp. who was diagnosed by computed tomography (Cn scan, serological findings, and/or fecal examination. The patient was a 43-year-old Korean female and was admitted to Kyung Hee University Hospital with the complaints of fever and abdominal pain. On admission, marked eosinophilia was noted in her peripheral blood. CT scan showed specific lesions for clonorchiasis and fascioliasis in the liver, along with lesions suggestive of amebic abscess. Micro-ELISA revealed positive results for the 2 helminthic infections. Eggs of C. sinensis and trophozoites of Entamoeba histo/ytica were observed in the stool. Treatment with praziquantel followed by metronidazole and tinidazole reduced abnormalities in the liver and eosinophilia. This is the first case report of a possible co-infection with 2 kinds of liver flukes in the Republic of Korea.

Bioassays of Polycyclic Aromatic Hydrocarbons Using cyp1a1-Luciferase Reporter Gene Expression System in Mouse Liver Hepa 1 Cells

  • Min, Kyung-N.;Kim, Ja-Y.;Sheen, Yhun-Y.
    • Environmental Mutagens and Carcinogens
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    • v.23 no.1
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    • pp.30-34
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    • 2003
  • Recent industrial society has human widely exposed to PAHs (polynuclear aromatic hydrocarbons) that are comming from the incomplete combustion of organic material as wider spread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. Our laboratory have been studied the effect of PAHs in the mouse liver hepa 1 cells. In this study, we examined the mouse liver hepa-l cells as a new bioassay system to evaluate bioactivity of PAHs. We have selected 13 PAHs to examine bioassay using cyp1a1-luciferase reporter gene expression system where cyp1a1 1.6 Kb 5flanking region DNA was cloned in front of luciferase reporter gene and this plasmid was transfected into hepa 1 cells transiently. This cells then used for the study to observe the effect of PAHs. We demonstrated that PAHs induced the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase (EROD) activities in a concentration-dependant manner. Some of PAHs showed stronger stimulatory effect on CYP1 gene expression than TCDD. Acenaphthene, anthracene, fluorine, naphthalene, pyrene, phenanthrene, carbazole were weak responders to cyp1a1 promoter activity stimulation and EROD induction in hepa 1 cells and these chemicals seemed to respond less to EROD than cyp1a1 promoter activity. Benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, and dibenzo(a,h)anthracene showed strong response to cyp1a1 promoter activity stimulation and also EROD induction in hepa 1cells. Results of dose response study suggested that four strong responding PAHs, such as benzo(a)anthracene benzo(k)fluoranthene, chrysene, and dibenzo(a, h)anthracene might be mediated through arylhydrocarbon receptor system in hepa1 cells.

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Measurement of Normal Gastric Emptying Rate Using Chicken Liver Labeled with $^{99m}Tc-Colloid$ (정상인의 Gastric Emptying Rate 측정)

  • Lee, Cheorl-Woo;Kim, Chahng-Guhn;Kim, Byung-Chan;Won, Jong-Jin;Nah, Yong-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.22 no.2
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    • pp.193-197
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    • 1988
  • Measurement of gastric emptying rate has been performed by a variety of techniques. Nuclear medicine method is a major advance in the quantitative evaluation of gastric function and also of pharmacologic intervention. Normal gastric emptying rate was measured in 48 healthy volunteers using live chicken liver labeled with $^{99m}Tc-Tin$ Colloid as a solid phase marker. In vitro studies were performed to evaluate the labeling efficiency and stability in hydrochloric acid and in human gastric juice of intracellularly labeled chicken liver. Anterior image counts only were compared with the geometric mean of anterior and posterior counts in 12 healthy volunteers who were studied by both anterior count and posterior count. The results were as follows: 1) The labeling efficiency in gastric juice and hydrochloric acid were $95.5{\pm}1.23%,\;95.7{\pm}1.15%$, respectively. 2) Half gastric emptying time by anterior count only was $126{\pm}21$ minutes 3) Although standard deviation of geometric mean method was smaller than anterior count method, gastric emptying curves from both method were similar. In daily practice, anterior count method may be useful alternative to geometric mean method in evaluation of gastric emptying rate.

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Hepatoprotective Effect of Fermented Artemisia princeps PAMPANINI by Lactic Acid Bacteria (발효강화쑥의 간장해 보호효과)

  • Choi, Hyuck-Jae;Kim, Eun-Jin;Han, Myung-Joo;Baek, Nam-In;Kim, Dong-Hyun;Jung, Hae-Gon;Kim, Nam-Jae
    • Korean Journal of Pharmacognosy
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    • v.38 no.3 s.150
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    • pp.245-253
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    • 2007
  • Artemisia princeps PAMPANINI has been used in traditional medicine of the treatment of inflammatory, liver dysfunction and order disorder in the far east countries including Korea. The present study was carried out to investigate the hepatoprotective effects of ethanol extract of Artemisia princeps (AP) and its fermented agents (AP-F) by lactic acid bacteria derived from human intestinal bacteria on liver injured rat induced by $CCl_4$ and d-galactosamine. Hepatoprotective activity was monitored by estimating serum ALT, AST, ALP, LDH, superoxide dismutase (SOD), glutathione redeuctase (GR) and glutathione peroxidase (Gpx) activities in the liver injured by hepatotoxin. Pretreating rats with AP or AP-F at the same dosage regimen significantly suppressed the acute elevation of serum transaminase, ALP, LDH and GR activities, and significantly increased the lowering of blood SOD and GR activites induced by hepatoxin. Based on these findings, it is presumed that AP and APF may have the hepatoprotective effect on $CCl_4$ and d-galactosamine-induced hepatotoxicity rat.

Effects of Cordyceps militaris on $CCl_4$ - Induced Liver Damage and Cancer Cell (HepG2 Cell) Growth (동충하초가 사염화탄소로 유발된 간 손상 및 간암세포증식에 미치는 영향)

  • Kim San;Hwang Choong yeon;Kim Nam kwen;Park Min cheul;Kim Jin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.4
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    • pp.684-692
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    • 2002
  • Cordyceps militaris has been known as a Chinese traditional medicine for the treatment of tuberculosis, asthma, kidney disease, debility and fatigue etc. This study was attempted to investigate the therapeutic effect of C. militaris extract on the cytotoxic activity of HepG2, human hepatocellular carcinoma cells and the liver damage induced by carbon tetrachloride in SD rats. C. militaris extracts inhibited significantly the proliferation of HepG2 cells in vitro. Carbon tetrachloride(CCl₄) caused a significant an increase in liver weight, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activity, alkaline phosphatase(ALP), serum thiobarbituric acid reactive substances (TBARS), microsomal TBARS, and decrease in microsomal detoxification enzymes (cytochrome P-450, P-450 reductase, cytochrome b5, b5 reductase). TBARS and ALP in serum pretreated with C. militaris extracts (300mg/kg/day, 600mg/kg/day) was significantly reduced compared to control group(CCl₄). Cytochrome b5 and b5 reductase activities were significantly increased in CM300 (300 mg/kg/day) and CM600 group(600 mg/kg/day), and cytochrome P-450 reductase was significantly increased in CM300 group. Pretreatment (100, 300, and 600 mg/kg/day for 7 days) of C. militaris with CCl₄ was significantly inhibited the accumulation microsomal TBARS and the significantly increased in the cytochrome P-450 activity. These results suggested that C. militaris (300mg/kg/day for 7 days) has appreciable therapeutic effect on CCl₄ induced hepatotoxicity.

Effect of Lactobacillus fermentum MG590 on Alcohol Metabolism and Liver Function in Rats

  • Kim, Ji-Hyun;Kim, Hyun-Jin;Son, Jeong-Hwa;Chun, Ho-Nam;Yang, Jin-Oh;Choi, Sung-Jin;Paek, Nam-Soo;Choi, Gyoung-Hoon;Kim, Sung-Koo
    • Journal of Microbiology and Biotechnology
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    • v.13 no.6
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    • pp.919-925
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    • 2003
  • Alcohol consumption has numerous health consequences for the human body. For example, heavy drinking on a daily basis causes liver diseases, and certain products such as acetaldehyde produced from alcohol metabolism are more toxic than alcohol itself. Accordingly, the current study evaluated the role of Lactobacillus fermentum MG590 to enhance the removal of the toxic effect of alcohol in alcohol metabolism. The maximum activities of the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) by L. fermentum MG590 were observed after 6 h of culture. The production of ADH and ALDH by L. fermentum MG590 was also confirmed by SDS-PAGE. Six hours after the addition of alcohol to a culture broth of L. fermentum MG590, the alcohol concentration decreased from 7.5 to 2.7%. From an in vitro evaluation based on hepatocytes, the viability of hepatocytes in a medium containing alcohol and the cytosol of L. fermentum MG590 was higher than that in a medium containing only alcohol. From an in vivo test using SD rats fed a 22% alcoholic drink, the blood alcohol concentration (BAC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) in the rats fed a medium containing L. fermentum MG590 were lower than those in the rats fed a medium containing only the alcohol drink. These results demonstrate that the ADH and ALDH produced by L. fermentum MG590 play an important role in detoxicating alcohol in vivo. Therefore, a fermentation broth of L. fermentum MG590 could be used as an effective alcohol detoxification drink.

Time-Dependent Hepatic Proteome Analysis in Lean and Diet-Induced Obese Mice

  • Oh, Tae-Seok;Kwon, Eun-Young;Choi, Jung-Won;Choi, Myung-Sook;Yun, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • v.21 no.12
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    • pp.1211-1227
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    • 2011
  • C57BL/6J mice have been widely used as a diet-induced obesity model because they trigger common features of the human metabolic syndrome. In the present study, C57BL/6J male mice were fed either a high-fat diet (HFD) or normal diet (ND) during a 24-week period, and then the age-dependent liver proteome of mice in two groups was analyzed using 2-DE combined with MALDI-TOF-MS. Among identified proteins, up-regulated proteins were subdivided to early (during the first 4 weeks) and late (20~24 weeks) markers that played a role in diet-induced obesity development. Important early markers included ketohexokinase and prohibitin, and late markers included the 75 kDa glucose-regulated protein, citrate synthase, and selenium-binding liver protein. Of these, the 75 kDa glucosere-gulated protein has already been linked to obesity; however, prohibitin protein involved in obesity was identified for the first time in this study. In order to validate the proteomic results and gain insight into metabolic changes between the two groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combined results of proteomic analysis with Western blot analysis revealed that antioxidant enzymes were progressively decreased, whereas cytoskeletal proteins were time-dependently increased in HFD mice.

Conjugated Linoleic Acid as a Key Regulator of Performance, Lipid Metabolism, Development, Stress and Immune Functions, and Gene Expression in Chickens

  • Choi, Yang-Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.3
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    • pp.448-458
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    • 2009
  • It has been well documented from animal and human studies that conjugated linoleic acid (CLA) has numerous beneficial effects on health. In chickens, CLA exerts many effects on performance ranging from egg quality and yolk lipids to meat quality. Although there are several CLA isomers available, not all CLA isomers have the same incorporation rates into egg yolk: cis-9,trans-11 and trans-10,cis-12 CLA isomers are more favorably deposited into egg yolk than other isomers investigated, but of the two isomers, the former has a higher incorporation rate than the latter. CLA alters the amounts and profiles of lipids in plasma, muscles and liver. Furthermore, increased liver weight was reported in chickens fed dietary CLA. As observed in egg yolk, marked reduction in intramuscular lipids as well as increased protein content was observed in different studies, leading to elevation in protein-to-fat ratio. Inconsistency exists for parameters such as body weight gain, feed intake, feed conversion ratio, egg production rate and mortality, depending upon experimental conditions. One setback is that hard-cooked yolks from CLA-consuming hens have higher firmness as refrigeration time and CLA are increased, perhaps owing to alterations in physico-chemistry of yolk. Another is that CLA can be detrimental to hatchability when provided to breeders: eggs from these breeders have impaired development in embryonic and neonatal stages, and have increased and decreased amounts of saturated fatty acids and monounsaturated fatty acids (MUFAs), respectively. Thus, both problems can be fully resolved if dietary sources rich in MUFAs are provided together with CLA. Emerging evidence suggests that CLA exerts a critical impact on stress and immune functions as it can completely nullify some of the adverse effects produced by immune challenges and reduce mortality in a dose-dependent manner. Finally, CLA is a key regulator of genes that may be responsible for lipid metabolism in chickens. CLA down-regulates both expression of the gene encoding stearoyl-CoA desaturase-1 and its protein activity in the chicken liver while up-regulating mRNA of sterol regulatory element-binding protein-l.