• Title/Summary/Keyword: Acute liver injury

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Effect of Rheum undulatum Linne extract and Glycyrriza uralensis Fischer extract against arachidonic acid and iron-induced oxidative stress in HepG2 cell and CCl4-induced liver injury in mice (대황과 감초 병용의 항산화 및 간보호효과)

  • Lee, Eun Hye;Baek, Su Youn;Kim, Kwang-Youn;Lee, Seul-Gi;Kim, Sang Chan;Lee, Hyeong Sik;Kim, Young Woo
    • Herbal Formula Science
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    • v.24 no.3
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    • pp.163-174
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    • 2016
  • Objectives : Rheum undulatum Linne and Glycyrriza uralensis Fischer are widely used herbal medicine. In this study, anti-oxidant and liver protective effects of R. undunlatum extract (RUE) and G. uralensis extract (GUE) were investigated in HepG2 cells, respectively. Oxidative stress and liver fibrosis were induced by arachidonic acid (AA) and iron, and CCl4.Methods : MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of apoptosis related proteins. In addition, reactive oxygen species (ROS) and mitochondrial dysfunction were measured. In vivo, BALB/c mouse were orally administrated with the aqueous extract of 10 mg/kg RUE and 100 mg/kg GUE for 3 days and then, injected with CCl4 0.5 ml/kg body weight to induce acute liver damage. Serum ALT level was measured, and histological change was observed in Harris's hematoxylin and eosin stainResults : RUE and GUE pre-treatment increased relative cell viability in concentration dependent manner and altered the expression levels of apoptosis-related proteins such as procaspase 3, PARP and Bcl-xL. RUE and GUE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species (ROS) production induced by AA and iron. In addition, RUE and GUE activated liver kinase B1 (LKB1), by increasing phosphorylation. Moreover, RUE and GUE treatment decreased liver injuries induced by CCl4, as evidenced by decreases in histological liver damage as well as serum alanine amino transferase (ALT) level.Conclusions : These data suggest that RUE and GUE has anti-oxidant and liver protective effects against AA and iron-induced oxidative stress and CCl4-induced liver injury.

Inhibitory Effects of Chimeric Decoy Oligodeoxynucleotide in the Regulation of Transcription Factors NF-κB and Sp1 in an Animal Model of Liver Cirrhosis (간경화 동물모델에서 Chimeric decoy oligodeoxynucleotide로 억제되는 NF-κB와 Sp1 전사인자 발현 억제 효과에 대한 연구)

  • Kim, Kyung-Hyun;Park, Ji-Hyun;Kim, Soo-Jung;Lee, Woo-Ram;Chang, Young-Chae;Kim, Hyun-Chul;Park, Kwan-Kyu
    • Journal of Life Science
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    • v.19 no.10
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    • pp.1360-1367
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    • 2009
  • Liver fibrosis is a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. To develop a novel therapeutic approach in hepatic fibrogenesis, we examined the simultaneous suppression of the transcription factors NF-$\kappa$B and Sp1, which regulate acute inflammation and continuous deposition of extracellular matrix in liver fibrosis. We employed chimeric decoy oligodeoxynucleotide containing the consensus sequences of both NF-$\kappa$B and Sp1 binding sites, to suppress these transcription factors simultaneously. Treatment of chimeric decoy oligodeoxynucleotide reduced the activity of hepatic stellate cells in vitro, and decreased the expression of fibrotic and proinflammatory gene responses in a mouse model of liver fibrosis. These results suggest that chimeric decoy oligodeoxynucleotide strategy can be a potential therapeutic application to prevent liver fibrosis.

A Case of Interstitial Pneumonitis with Acute Live Injury Caused by Herbal Medicine Made from Golden Thread (황련으로 만든 한약 복용 후 발생한 급성 간손상을 동반한 간질성 폐렴 1예)

  • Jhun, Byung-Woo;Kim, Da-Min;Park, Ji-Hyeon;Jung, Hyun-Ae;Song, Lim-Hwa;Han, Joung-Ho;Chung, Man-Pyo
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.6
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    • pp.470-475
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    • 2011
  • So far more than 350 drugs have been reported to be the cause for lung injury and the incidence tends to increase. Although infiltrative lung disease is the most common pattern of drug-induced lung injury, it can appear in the form of alveolar changes, vasculitis and other injury. Herbal medicine also has been known as a cause for interstitial pneumonitis, but it is difficult to identify the key herbal medicine because of the complex components of the contents. Till date, there is no report of pneumonitis caused by golden thread. Here we report a case of a 54-year-old male who developed interstitial pneumonitis with acute liver injury caused by herbal medicine made from golden thread.

Effect of fermented Hovenia dulcis Thunb fruit water extract on biomarker for liver injury and body weight changes in rats given oral administration of ethanol (헛개열매추출액발효물이 흰쥐의 에탄올 경구투여에 의한 간손상 지표와 체중 감량 완화에 미치는 영향)

  • Choi, Ji-Young;Kim, Jun-Han;Kim, Gho;Kim, Choon-Kyung;Choi, Myung-Sook
    • Food Science and Preservation
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    • v.21 no.3
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    • pp.412-420
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    • 2014
  • This study was performed to investigate the effect of fermented Hovenia dulcis Thunb fruit water extract on biomarkers for acute (a) ethanol-induced hangover and chronic (c) ethanol-induced liver injury in rats. For acute ethanol-induced hangover, the rats were administered distilled water (D.W., 10 mL/kg body wt.), Hovenia dulcis Thunb fruit water extract (HWE, 400 mg/10 mL/kg body wt.) and fermented HWE (FHWE, 400 mg/10 mL/kg body wt.), respectively, before 40% ethanol (5 g/kg body wt.) was administered. For chronic ethanol-induced liver injury, the rats were randomly divided into the normal control (cNC), ethanol (cET), cET-HWE and cET-FHWE groups. The cNC and cET groups were administered D.W. (10 mL/kg body wt.) before 40% alcohol (5 g/kg body wt.) was administrered for 21 days. The cET-HWE and cET-FHWE groups were administered HWE (400 mg/10 mL/kg body wt.) and FHWE (400 mg/10 mL/kg body wt.), respectively before 40% ethanol (5 g/kg body wt.) administration for 21 days. For acute ethanol-induced hangover, the serum alcohol and acetaldehyde concentrations were more significantly reduced in the aHWE and aFHWE groups than in the aET group. Moreover, the effect of FHWE was greater than that of HWE. For chronic ethanol-induced liver injury, the serum ethanol, acetaldehyde, ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GTP) levels and the hepatic lipids concentration more significantly dropped in the cET-HWE and cET-FHWE groups than in the cET group. The FHWE administration showed faster recovery of the serum glucose concentration than in the cET and cET-HWE groups. The body weight reduction tended to normalize in the cET-HWE and cET-FHWE groups, which is ideal for chronic ethanol administration. These results suggest that FHWE has a protective effect against ethanol-induced liver damage, as evidenced by its ability to lower the serum ethanol and acetaldehyde concentrations after alcohol administration, and by its ability to decrease the level of ${\gamma}$-GTP and hepatic lipids. FHWE also elevated serum glucose concentration. Therefore, FHWE is effective in reducing ethanol-induced hangover and can play a beneficial role in the treatment of ethanol-induced liver damage as well as body weight reduction.

Protective Effects of Ethanol Extract of Allium hookeri Root on Acute Alcohol-Induced Intoxication in ICR Mice (급성 알코올 독성을 유발한 ICR Mouse에서 Allium hookeri 뿌리 에탄올 추출물의 간 기능 보호 효과)

  • Kang, Hae-Young;Lee, Cho-Eun;Ly, Sun-Yung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.5
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    • pp.625-633
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    • 2016
  • Allium hookeri is known as a healthy food since it contains larger amounts of sulfur compounds than commonly known alliaceous plants. The antioxidant and anti-inflammatory effects of A. hookeri were compared between two types of extracts, $80^{\circ}C$ water and 95% ethanol extracts of A. hookeri roots. A. hookeri root 95% ethanol extracts displayed superior total polyphenol content, antioxidant activity [1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical scavenging activity], and anti-inflammation activity than those of water extracts (P<0.05). We studied the effects of A. hookeri root 95% ethanol extracts (95% ethanol extracts group: AHE) on acute alcohol-induced intoxication in mice. AHE [250, 500, and 1,000 mg/kg body weight (BW)/d] was orally administered to the study group once a day for 1 week. On the last day of AHE treatment, 40% ethanol (10 mL/kg BW) was orally administered to induce acute liver injury. The blood alcohol concentration of mice treated with AHE was significantly lower compared to the control group (P<0.05). The levels of hepatic aspartate aminotransferase and alanine aminotransferase were lower in the AHE-treated group than the control group (P<0.05). The RT-PCR results for alcohol dehydrogenase and aldehyde dehydrogenase measured based on mRNA in liver tissues showed that enzyme activities were higher in the AHE-treated group than in the control group at a low blood alcohol concentration.

Effects of Oleanolic Acid and Hederagenin on Acute Alcohol-Induced Hepatotoxicity in Mice (마우스에서 Oleanolic Acid와 Hederagenin이 급성 알코올성 간독성에 미치는 효과)

  • Jung, Suhan;Lee, Sanghoon;Ko, Kwang Suk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.3
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    • pp.307-312
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    • 2016
  • We studied the effects of oleanolic acid and hederagenin on acute alcohol-induced hepatotoxicity in mice. Oleanolic acid [10 and 20 mg/kg body weight (BW)/d] or hederagenin (10 and 20 mg/kg BW/d) was orally administered to the study group for 1 week. On the last day of treatment, ethanol (5 g/kg BW) was orally administered to induce acute liver injury. The oleanolic acid-treated group showed lower levels of alanine aminotransferase compared to the ethanol-treated group (EtOH). The mRNA expression level of alcohol dehydrogenase was significantly increased in the high dosage oleanolic acid-treated group compared with the control and EtOH groups. The glutathione levels of the oleanolic acid or hederagenin-treated groups were elevated significantly compared with those of the control and EtOH groups. The mRNA expression levels of glutathione synthetic enzymes were also elevated in the oleanolic acid-treated groups. The oleanolic acid or hederagenin-treated groups also showed lower levels of mRNA expression of tumor necrosis factor alpha. Thus, these results show that oleanolic acid and hederagenin could reduce oxidative stress and hepatotoxicity in ethanol-treated mouse liver.

Effects of Cadmium and Zinc Pretreatment on the Acute Cadmium Toxicity and Metallothionein Induction in Rats (카드뮴 및 아연 전처리가 흰쥐의 급성카드뮴 중독 및 Metallothionein생성에 미치는 효과)

  • 이재형;염정호;강현철;김남송;고대하;기노석
    • Journal of Environmental Health Sciences
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    • v.21 no.3
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    • pp.1-15
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    • 1995
  • Tolerance to toxic effects of cadmium(Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats(A, B, C), each consisting of 52 rats, were studied and each group was divided into three subgroups(1,2,3), 28 rats for each subgroup. Rats were subcutaneously pretreated with saline(A), $CdCl_2$(0.5 mg/kg, B), and $ZnCl_2$(13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with $CdCl_2$(3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after 1,3,5,6 days of pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target-organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggest that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretreatment, served to induce the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

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Study on the hepatoprotective effects of lemon balm and dandelion leaf extract combination in carbon tetrachloride-mediated liver injured mice (사염화탄소 유도성 급성 간 손상 모델에서 레몬밤과 민들레 잎 추출물의 혼합 비율에 따른 간 보호 효능 연구)

  • Choi, Beom-Rak;Cho, Il Je;Jung, Su-Jin;Kim, Jae Kwang;Lee, Dae Geon;Ku, Sae Kwang;Park, Ki-Moon
    • Herbal Formula Science
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    • v.27 no.3
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    • pp.199-211
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    • 2019
  • Objectives : Present study investigated the hepatoprotective effects of various combinations of lemon balm and dandelion (LD) leaf extract on carbon tetrachloride ($CCl_4$)-induced acute liver injury. Methods : Mice were orally treated with 200 mg/kg of LD extracts [1:1, 1:2, 1:4, 1:6, 1:8, 2:1, 4:1, 6:1, or 8:1 (weight : weight)] for 7 days, and then intraperitoneally injected with $CCl_4$ (0.5 mL/kg). Silymarin (100 mg/kg) was used as reference drug. Body weight gain, relative liver weight, serum biochemistry, histopathologic analyses, and hepatic antioxidant system were examined to elucidate the fittest combination ratio of LD extract. Results : All varying combinations of LD extract significantly increased body weight gain and decreased relative liver weight by $CCl_4$. In addition, LD extract reduced serum aspartate aminotransferase and alanine aminotransferase. Histopathological analyses indicated that LD extract significantly decreased histological activity index score, degenerated hepatocytes, and infiltrated inflammatory cells induced by $CCl_4$. Moreover, LD extract reduced lipid peroxidation, and attenuated the reduction of hepatic glutathione, superoxide dismutase, and catalase by $CCl_4$. Although there were no statistical differences in body weight gain between silymarin- and LD extract-treated groups, administration of 1:1, 2:1, and 4:1 combination of LD extract exhibited more favorable hepatoprotective effects than silymarin. Especially, 2:1 combination of LD extract showed the most potent hepatoprotective effects. Conclusion : Of various combinations of LD extract tested, present results suggest that 2:1 combination of LD extract would be a promising herbal formulation to protect liver from oxidative stress.

Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice

  • Park, Chung Mu;Song, Young-Sun
    • Nutrition Research and Practice
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    • v.13 no.6
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    • pp.473-479
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    • 2019
  • BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and $10{\mu}g/kg\;BW$, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and $TNF-{\alpha}$ levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor $(NF)-{\kappa}B$ and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.