• Title/Summary/Keyword: Liver cell damage

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SKT + EKE (2:1) protects oxidative stress induced-liver damage (산화적 스트레스에 대한 생간건비탕가음양곽(生肝健脾湯加淫羊藿) (2:1)의 간보호효과)

  • Sang Mi Park;Dae Hwa Jung;Hyo Jeong Jin;Ye Lim Kim;Kyung-soon Kim;Min Hwangbo;Sang Chan Kim
    • Herbal Formula Science
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    • v.32 no.1
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    • pp.63-82
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    • 2024
  • Objective : Saengkankunbi-tang (SKT) is used as a traditional Korean herbal formula for treatment of liver diseases. We investigated the hepatoprotective effects of SKT plus Epimedium koreanum Nakai (EKE) against arachidonic acid (AA) + iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4)-mediated acute liver damage in mice. Methods : The cyto-protective effects of SKT + EKE were determined by MTT assay, western blot and fluorescence activated cell sorting analysis. In mice, blood biochemistry and western blot were assessed in CCl4-induced acute hepatic damage. The animal groups included vehicle-treated control, CCl4, SKT (200 mg/kg/day), EKE (100 mg/kg/day), SKT (200 mg/kg/day) + EKE (100 mg/kg/day) and silymarin (200 mg/kg/day). Results : In HepG2 cells, pretreatment with SKT + EKE significantly suppressed cytotoxicity induced by AA + iron and reduced the expression of proteins related to apoptosis. In addition, pretreatment with SKT + EKE significantly prevented the increase in H2O2 production, GSH depletion, and lower mitochondrial membrane potential induced by AA + iron. In CCl4-induced liver damage mice, the administration of SKT + EKE prevented the liver damage by inhibition of hepatocyte damage and expression of apoptosis proteins in liver. More importantly, in vitro and in vivo assay, SKT + EKE showed significant effect compare with SKT alone or EKE alone in all parameters. Conclusions : These results indicated that SKT + EKE could protect against oxidative stress-induced liver damage, and SKT + EKE is more effective than SKT alone or EKE alone.

Effects of Taeumjowetang on Lipid Peroxidation by Free Radicals and Oxidative Damage of Hepatocytes by tert-Butyl Hydroperoxide (태음조위탕(太陰調胃湯)의 항산화(抗酸化) 효능(效能)에 의한 간세포(肝細胞) 보호(保護) 효과(效果)에 관한 연구(硏究))

  • Kim, Man-woo;Park, Seong-sik
    • Journal of Sasang Constitutional Medicine
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    • v.13 no.1
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    • pp.51-60
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    • 2001
  • Effects of Taeumjowetang on Lipid Peroxidation by Free Radicals and Oxidative Damage of Hepatocytes by tert-Butyl Hydroperoxide. 1. Purpose The present study was carried out to evaluate the antioxidant effects of Taeumjowetang in vitro. 2. Methods In this study, antioxidant effects of TJT on lipid peroxidation were determined according to the method of TBA. (Abbreviation) TJT : Taeumjowetang, TBA : 2-thiobarbituric acid. 3. Results : 1) TJT inhibited markedly peroxidation of linoleic acid during the autoxidation. 2) TJT inhibited lipid peroxidation induced by hydroxyl radical derived from H2O2-Fe2+ in rat liver homogenate. 3) TJT showed 66% scavenging effect on DPPH radical. 4) TJT exhibited a 25% inhibitory effect on superoxide generation from xanthine-xan thine oxidase system. 5) To investigate the antioxidative effects of TJT on the hepatocytes, cultured normal rat liver cells(Ac2F) were prepared and incubated with or without TJT. After 16~18hr, cells placed in DMEM medium without serum, and then incubated with 1mM t-BHP for 2hr. Viable cells were detected by MTT assay. In this test, TJT protected the cell death induced by t-BHP and significantly increased cell viability in the normal rat liver cell. (Abbreviation) DPPH : ${\alpha},{\alpha}$-diphenyl-${\beta}$-picryl hydrazyl, DMEM : Dulbecco's Modified Eagle Medium, t-BHP : terr-butyl hydroperoxide, 4. Conclusion These results suggested that TJT might play a protective role in lipid peroxidation by free radicals.

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The Natural Killer Cell Response to HCV Infection

  • Ahlenstiel, Golo
    • IMMUNE NETWORK
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    • v.13 no.5
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    • pp.168-176
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    • 2013
  • In the last few years major progress has been made in better understanding the role of natural killer (NK) cells in hepatitis C virus (HCV) infection. This includes multiple pathways by which HCV impairs or limits NK cells activation. Based on current genetic and functional data, a picture is emerging where only a rapid and strong NK cell response early on during infection which results in strong T cell responses and possible subsequent clearance, whereas chronic HCV infection is associated with dysfunctional or biased NK cells phenotypes. The hallmark of this NK cell dysfunction is persistent activation promoting ongoing hepatitis and hepatocyte damage, while being unable to clear HCV due to impaired IFN-${\gamma}$ responses. Furthermore, some data suggests certain chronically activated subsets that are $NKp46^{high}$ may be particularly active against hepatic stellate cells, a key player in hepatic fibrogenesis. Finally, the role of NK cells during HCV therapy, HCV recurrence after liver transplant and hepatocellular carcinoma are discussed.

Effect of a Static Magnetic Field on Susceptibility to Ethanol-Induced Hepatic Dysfunction in Rats

  • Park, Kap-Joo;Kim, Eun-Jung;Cho, Myung-Hwan;Lee, Jae-Seok
    • Food Science and Biotechnology
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    • v.15 no.6
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    • pp.833-837
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    • 2006
  • To determine whether alcohol-treated rat liver cells can be protected by a static magnetic field (SMF), we analyzed the blood chemistry and histology of hepatic tissue removed from alcohol-exposed rats that had been exposed to a static magnetic field. The rats were exposed to a 0.3 tesla (3,000 gauss) magnetic field (MF) for 24 hr daily for 5 weeks with appropriate controls. Glutamic pyruvic transaminase activity and the triglyceride levels in animals exposed to the north (N) or south (S) pole of the MF decreased significantly (p<0.01 and p<0.05, respectively) compared with negative control animals with alcohol exposure. A histological examination of hepatic tissue revealed a moderate to severe accumulation of fat vacuoles of various sizes in the cytoplasm of the hepatocytes of animals in the negative control group throughout the study; whereas in groups exposed to the MF poles, fewer fat vacuoles were seen compared with the negative control group. Electron microscopic observations showed that exposure to the N or S pole protected organelles, including the nucleus, from damage during exposure to this toxic agent, as indicated by the fact that the nucleus and the mithochondria virtually retained their shape throughout this study. These results suggest that exposure to a SMF could be an excellent way of protecting against alcohol-induced damage to the rat liver cell.

Histological analysis of five organs in streptozotocin-induced diabetic rats (Streptozotocin 유도 당뇨 흰쥐에서 주요 장부 간 조직학적 변화 비교 연구)

  • Oh, Tae Woo;Kang, Seok Yong;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.28 no.6
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    • pp.39-45
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    • 2013
  • Objectives : This study was conduct to compare of histological changes on four target organs which related with diabetes in streptozotocin-induced diabetic rats. Methods : Diabetes was induced in male Sprague-Dawley rats by consecutive injection of streptozotocin (STZ) at different doses of 30, 40 and 50 mg/kg for 5 days. After 4 weeks, all rats were sacrificed, five different organs such as pancreas, liver, kidney, and lung were isolated and observed their histological changes by hematoxylin and eosin (H&E), Periodic acid-Schiff (PAS) and Masson's trichrome staining. The changes of body weight, blood glucose, and food and water intake were also measured. Results : The multiple administration of STZ was induced diabetes in rats with hyperglycemia, decrease of body weight, increase water and food intake, and histopathological changes of target organs, compared with those of normal rats in both dose-dependent and time-dependent manner. In histological analysis, pancreas was showed decrease of the islet numbers with beta-cell loss. Kidney showed morphological damage with glomerulus hypertrophy, and also lung was showed bronchial epithelial damage with inflammatory cells infiltration. In liver, the portal vein and hepatic artery could not observed, and showed inflammatory cell infiltration with liver fibrosis. Conclusions : These results suggest that the increase of the capacity of STZ, each of the more chronic disease, it can be seen that the damage was deep. Thus, evaluate the resulting drug appropriate depending on the purpose of the model is expected to be selected.

Anti-Myelosuppression Effects of Korean Red Ginseng in SD Rat Injected with 5-fluorouracil

  • Park, Hye-Jung;Han, Jong-Min;Kim, Hyeong-Geug;Choi, Min-Kyung;Lee, Jin-Seok;Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.33 no.2
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    • pp.47-55
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    • 2012
  • Objectives: This study aimed to investigate the preventive effect of red ginseng (RG) on 5-fluorouracil (5-FU)-induced side effects focusing on myelosuppression. Methods: Rats (n = 50) were divided into five groups, nave, control (ip, 5-FU injection of 150 mg/kg), and RG pre-treatment (po, 25, 50 and 100 mg/kg for 5 days before 5-FU injection). On the $7^{th}$ day after 5-FU injection, we evaluated the effects using peripheral hematological parameters, colony-forming assay, cytokine levels and histopathological finding. Results: The peripheral white blood cell and the differential count were dramatically suppressed by 5-FU, while RG (50 and 100 mg/kg) treatment significantly improved total white blood cell, neutrophil, lymphocyte and platelet counts. Also, RG (100 mg/kg) pre-treatment significantly increased the number of CFU-GM colony compared with the control group. RG pre-treatment also ameliorated the histopathological damage in bone marrow, spleen, stomach and small intestine tissue. Conclusions: These results demonstrate that Korean RG has preventive effects against 5-FU-induced myelotoxicity and gastrointestinal damage.

Metronidazole Reduced Ammonia Toxicity in Human Hep G2 cell and Rat Hepatocytes (Hep G2 세포와 rat 간세포에서 Metronidazole에 의한 암모니아 독성 감소)

  • Kim, Bo-Ae;Kim, Hyun-Jung;Kim, You-Young
    • KSBB Journal
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    • v.23 no.5
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    • pp.381-386
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    • 2008
  • Lipophilic ammonia is toxic gas and can easily diffuse across cell membranes. Excess ammonia is implicated in the pathogenesis of several metabolic disorders including hepatic encephalopathy and may result in the death. The purpose of this study was to clarify the inhibition effect of metronidazole on liver cell damage due to ammonia in human Hep G2 cell and rat hepatocytes. The effects of metronidazole were studied in ammonium chloride treated human Hep G2 cell (75 mM) and rat hepatocyte (100 mM) following $0.1{\mu}M$ metronidazole treatment. In MTZ+AC group, cell viabilities increased prominently and LDH activities decreased over 25% than AC group. Furthermore, ammonia level according to ammonium chloride treatment reduced over 30% and lipid peroxidation as an index of cell membrane damage decreased more than twice. By comparison with control, catalase activity showed more than 30% reduction in AC group while less than 10% reduction in MTZ+AC group, respectively. In addition, MTZ+AC group showed the similar cell structure as control in cell morphology study by using light microscope, and represented fluorescent intensity decrement compared with AC group in fluorescent microscopic study with avidin-TRITC fluorescent dye. And cleaved PARP expression due to ammonia reduced twofold or more in MTZ+AC group. As the results suggest, metronidazole may protect the liver cell by inhibiting cell damages due to ammonia and be used for an effective antagonist of ammonia in hyperammonemia.

The Effects of Chungganhaeju-tang (Qingganjiejiu-tang) on Alcoholic Liver Damages by Applying Proteomics (청간해주탕(淸肝解酒湯)이 알코올성 간손상 Proteome에 미치는 영향)

  • Jung, Yun-Jong;Kim, Young-Chul;Woo, Hong-Jung;Lee, Jang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.28 no.1
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    • pp.68-79
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    • 2007
  • Objectives : The purpose of our study was to investigate the effects of Chungganhaeju-tang (Qingganjiejiu-tang) on alcoholic liver damage by applying proteomics. Materials and Methods : Sprague-Dawley rats were used in this experiment; the rats were divided into a control group, alcohol group and Chungganhaeju-tang + alcohol group. Ethanol was orally administered twice a day for 4 weeks to the alcohol group. Water without ethanol was administered twice a day for 4 weeks to the control group. Ethanol + Chungganhaeju-tang extract was orally administered twice a day for 4 weeks to the Chungganhaeju-tang + alcohol group. The livers of each group were processed and we investigated histology, OxyBlot, 2-dimensional electrophoresis, and western blot of liver of each group. Results : In the histological findings of the liver, the alcohol group showed portal fibrosis with a few septa or without septa. The Chungganhaeju-tang + alcohol group showed no fibrosis or portalfibrosis without septa. In the OxyBlot finding, Chungganhaeju-tangprevented liver damage by oxidation. In the 2-dimensional electrophoresis finding, formiminotransferase cyclodeaminase (FTCD), glucose regulated protein, 58 kDa (GRP58K), aryl sulfotransferase, sulfotransferase family 1A, member 2, similar to acyl-coenzyme A oxidase-like, and catalase were changed. Conclusion : Chungganhaeju-tangexerts an inhibitory effect against the fibrosis and oxidation induced by alcohol in rat liver cell, and some proteins induced by alcohol were changed by Chungganhaeju-tang.

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The Protective Effects of Scutellaria baicalensis Georgi Water Extracts on the Immunomodulatory Effects on Liver Damage Induced by Carbon Tetrachloride in Rats (사염화탄소로 간 손상이 유발된 흰쥐에서 황금(黃芩) 열수 추출물이 면역작용에 미치는 효과)

  • An, Chi-Sun;Jin, Hai-Lan;Jeon, Yun-Hui;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.4
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    • pp.273-279
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    • 2009
  • GATA-binding protein-3 (GATA-3) and T-box expressed in T-cells (T-bet) are now considered as master transcription factors involving Th cell differentiation, but the roles of these factors are still uncertain in vivo. This study was conducted to investigate the expression of these transcription factors in the liver damage induced by carbon tetrachloride ($CCl_4$) in rats. In this study, liver damage were induced with Scutellaria baicalensis Georgi water extracts (SBW) and followed for 4 weeks. The expression of GATA-3 and T-bet protein in liver damage induced by $CCl_4$ and the serum levels of immunoglobulin A (IgA), IgE were studied after 4 weeks of treatment. We found that effect of SBW on IFN-$\gamma$, STAT1, pSTAT1 and T-bet was decreased in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. $CCl_4$+SBW group was significantly lower than $CCl_4$ group in IL-4, STAT6, pSTAT6 and GATA-3. Our data indicate that cytokine protein production were increased in $CCl_4$ group and $CCl_4$+SBW group. From these results, water extracts obtained from Scutellaria baicalensis Georgi may have an immunoregulatory effect in the liver induced by $CCl_4$ of rats.

Plasma, Tissue Thiobarbituric Acid Reactive Substance and Lymphocyte Oxidative DNA Damage in Mouse Fed Gamma Irradiated Diet (방사선 조사 사료를 섭취한 Mouse의 혈장, 간, 소장 점막의 과산화지질과 림프구 DNA의 산화적 손상)

  • 장현희;강명희;양재승;이선영
    • Journal of Nutrition and Health
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    • v.36 no.3
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    • pp.255-261
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    • 2003
  • Food irradiation has been steadily increasing in many countries in line with increasing international trade and concerns about naturally occurring harmful contaminants in food. Although irradiation provides an excellent safeguard for the consumer by destroying almost 100% of harmful bacteria, it is necessary to ensure the safety of irradiated foods. This study was performed to investigate the effect of an irradiated diet on lipid peroxidation in the plasma, liver, small intestinal mucosa, and lymphocyte DNA damage in mice. Eight-week old ICR mice were assigned to two groups to receive either non-irradiated or irradiated (10 kGy) diets containing 20.38% fish powder and 6.06% sesame seeds for 4 weeks. The resulting changes in the degrees of lipid peroxidation were evaluated based on the level of plasma and liver thiobarbituric acid reactive substance (TBARS), transmission electron micrograph of jejunal mucosa, and free radical-induced oxidative DNA damage in lymphocytes, as measured by alkaline comet assay (single cell gel electrophoresis). The peroxide values of the gamma irradiated diet were measured every week, and the sample for comet assay was taken at the end of the four week experimental period. There was no significant difference in food efficiency ratio between the two groups. The peroxide values of the diet were immediately increased to 35.5% after gamma irradiation and kept on increasing during storage. After 4 weeks, no differences in tissue or plasma TBARS value were observed between the two groups, but epithelial cells of jejumum showed osmiophillic laminated membranous structures, considered as myelin figures,. The oxidative DNA damage expressed as tail moment (TM) increased 30% in the blood lymphocytes of the mice fed the irradiated diet. In conclusion, the comet assay sensitively detected differences in lymphocyte DNA damage after feeding with the irradiated diet for 4 weeks. However, in order to ensure the safety of irradiated foods, it would be more useful to conduct a long-term feeding regimen using an irradiated diet and examine the level of lipid peroxidation and the state of oxidative stress in a greater range of organs.