• Title/Summary/Keyword: Hepatotoxicity

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Hepatoprotective effects of the aqueous extract from Taraxacum officinale (Dandelion) against Thioacetamide-induced hepatotoxicity in rats (Thioacetamide로 유발된 간 손상에 대한 Taraxacum officinale (Dandelion) 추출물의 효과)

  • Cho, In-Young;Ma, Se-Ryung;Moon, Sun-Jin;Yu, Do-Hyeon;Shin, Sung-Shik;Son, Chang-Ho;Oh, Ki-Seok;Hur, Tai-Young;Jung, Young-Hun;Choi, Chang-Yong;Suh, Guk-Hyun
    • Korean Journal of Veterinary Service
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    • v.36 no.4
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    • pp.233-242
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    • 2013
  • The genus Taraxacum, known by the common name Dandelion, is a medicinal herb in the family Asteraceae. It has been traditionally used as a folk medicine for the treatment or prevention of various diseases due to its anti-inflammatory and anti-oxidative properties. In this study, we attempted to evaluate protective effects of Dandelion related with anti-oxidative activity to Thioacetamide (TAA)-induced liver damage. 36 rats were randomly assigned to six experimental groups : Control, Dandelion water extract (DWE), TAA, TAA&DWE 300, TAA&DWE 600, TAA&DWE 1,200 groups. Rats in DWE and TAA&DWE groups were pretreated with DWE (300, 600 or 1,200 mg/kg BW) by gavage for 7 days. All rats were treated intraperitoneally with TAA (200 mg/kg BW) or normal saline at 12 hours after last oral administration and sacrificed at 12 hours after last treatment. Levels of WBC and Neutrophil count were significantly decresed in TAA&DWE 1,200 group compared with that in TAA group (P<0.05). In TAA&DWE 600 and TAA&DWE 1,200 groups, serum AST, ALT, GGT levels were lower than TAA group (P<0.05). The serum TG level was significantly elevated in TAA&DWE groups compared with those in TAA group. Liver tissues from TAA group showed extensive histopathological changes, characterized by moderate or severe hepatocytes degeneration, inflammatory cell infiltration, and congestion. In the TAA&DWE group, The severity of histopathological lesions were decreased compared to those in the TAA group. The MDA concentration was significantly decreased and GSH content was significantly increased in the TAA&DWE 1,200 group compared to those in the TAA group. GR, CAT and GST activities in the TAA&DWE 1,200 group were significantly increased compared to those in the TAA group.

Identification and quantification of major malonyl ginsenosides isolated from Panax ginseng C.A. Meyer (인삼(Panax ginseng C.A. Meyer)로부터 Malonyl ginsenoside의 분리 및 정량분석)

  • Shin, Woo Cheol;Jung, Jiyun;Na, Hyeon Seon;Bo, Jeon Hwang;Kim, Hyoung-Geun;Yoon, Dahye;Choi, Bo-Ram;Lee, Young-Seob;Kim, Geum-Soog;Baek, Nam-In;Lee, Yi;Lee, Dae Young
    • Journal of Applied Biological Chemistry
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    • v.62 no.4
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    • pp.375-384
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    • 2019
  • The root of Panax ginseng C.A. Meyer were extracted with 70% aqueous EtOH and the concentrates were partitioned into MeOH and H2O fractions using Diaion HP-20. The repeated SiO2 or octadecyl SiO2 column, and MPLC for the MeOH fraction led to isolation of four malonyl ginsenosides. The chemical structures of these compounds were determined as malonyl ginsenoside Rd (1) malonyl ginsenoside Rc (2) malonyl ginsenoside Rb2 (3) malonyl ginsenoside Rb1 (4) based on spectroscopic analyses including Nuclear magnetic resonance and HR-TOF/MS. The contents of malonyl ginsenoside Rb1 was highist as 5.44 mg/g of five years of ginseng. And malonyl ginsenoside Rd was lowest as 0.11 mg/g of six years of ginseng. Additionally, the malonyl ginsenoside Rd exhibited hepatoprotective effect against ethanol-induced hepatotoxicity in HepG2 cell line.

Isolation and quantitative analysis of metabolites from Scrophularia buergeriana and their hepatoprotective effects against HepG2 Cells (현삼 (Scrophularia buergeriana)에서 분리한 화합물의 함량분석 및 간세포 보호 효과)

  • Na, Hyeon Seon;Oh, Seon Min;Shin, Woo Cheol;Bo, Jeon Hwang;Kim, Hyoung-Geun;Yoon, Dahye;Yang, Seung Hwan;Lee, Young-Seob;Kim, Geum-Soog;Baek, Nam-In;Lee, Moon-Soon;Lee, Dae Young
    • Journal of Applied Biological Chemistry
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    • v.62 no.4
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    • pp.399-406
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    • 2019
  • The roots of Scrophularia buergeriana were extracted with 80% aqueous Methanol and the concentrates were partitioned into EtOAc, n-BuOH, and H2O fractions. The repeated silica gel or octadecyl SiO2column, and medium pressure liquid chromatographies for the n-BuOH fraction led to isolation of phenylethanoid glycosides and iridoid glycosides. The chemical structures of these compounds were determined as harpagoside (1), angoroside C (2), aucubin (3) and acetoside (4) based on spectroscopic analyses including nuclear magnetic resonance and MS. A simple and efficient HPLC with UV detection method for the simultaneous determination of the four compounds (1-4) has been developed and applied to their content determination in the S. buergeriana. The roots were extracted by 80% methanol, and the contents of 1, 2, 3, and 4 were determined to 11.5, 7.6, 41.2, and 4.8 mg/g, respectively. Additionally, angoroside C (2) and acetoside (4) exhibited hepatoprotective effect against ethanol-induced hepatotoxicity in HepG2 cell line.

Assessment of correlation between markers of ambient monitoring and biological monitoring of dimethylformamide for workers in synthetic leather manufacturing factories in Korea (국내 합성피혁제조업 근로자에 대한 디메틸포름아미드의 공기중 농도와 생물학적 노출지표간의 상관성 평가)

  • Hwang, Yang In;Lee, Mi-Young;Chung, Yun Kyung;Kim, Eun A
    • Analytical Science and Technology
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    • v.26 no.5
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    • pp.315-325
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    • 2013
  • The possibility of acute hepatotoxicity caused by dimethylformamide (DMF) requires regular monitoring of the workers who are using DMF to prevent the occupational disease. The authors performed ambient and biological monitoring of workers involved in synthetic leather manufacturing processes using DMF to assess the correlation between the markers of ambient and biological monitoring of DMF. The authors monitored 142 workers occupationally exposed to DMF from 19 workshops in the synthetic leather and ink manufacturing industries located in northern region of Gyeonggi-do. The subjects answered questionnaire on work procedure and use of personal protective equipment to be classified by exposure type. DMF in air samples collected using personal air samplers, diffusive and active sampler, was analysed using gas chromatograph-flame ionization detector (GC-FID) with DB-FFAP column (length 30 m, i.d. 0.25 mm, film thickness 0.25 ${\mu}m$). Urinary N-methylformamide (NMF) was analysed using gas chromatograph-mass selective detector (GC-MSD) at selected ion monitoring (SIM) mode with DB-624 column (length 60 m, i.d. 0.25 mm, film thickness 1.40 ${\mu}m$). Geometric mean (GM) and geometric standard deviation (GSD) of the ambient DMF was $6.85{\pm}3.43$ ppm, and GM and GSD of urinary NMF was $42.3{\pm}2.7$ mg/L. The ratio of subjects with DMF level over 10 ppm was 44%, and those with urinary NMF over 15 mg/L was 87%. NMF in urine adjusted by DMF in air was $4.61{\pm}2.57$ mg/L/ppm and $9.50{\pm}2.41$ mg/L/ppm, respectively, with or without respirator. There was seasonal differences of NMF in urine adjusted by DMF in air, $7.63{\pm}2.74$ mg/L/ppm in summer and $4.53{\pm}2.29$ mg/L/ppm in winter. The urinary NMF concentration which corresponds to 10 ppm of ambient DMF was 52.7 mg/L (r=0.650, n=128). Considering the difference of the route of exposure which resulted from the compliance of wearing personal protective equipment, the estimated contribution of respiratory and dermal exposure route for DMF was 48.5% vs. 51.5%.

Influence of Protaetia brevitarsis Extract on Liver Damage Induced by Carbon Tetrachloride and Ethanol in Rats (에탄올 및 사염화탄소의 긴 손상에 미치는 흰점박이꽃무지 추출물의 영향)

  • 이형철;황상구;강영국;손영옥;문자영
    • Journal of Life Science
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    • v.11 no.5
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    • pp.405-414
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    • 2001
  • Protaetia brevitarsis has been utilized as an ingredient of the description for the treatment of patients with chronic hepatic diseases in oriental medicine. This study was attempted to investigate whether Protaetia brevitarsis extract(PBE) protects or modulates the liver injuries induced by carbon tetrachloride or ethanol in Sprageue-Dawley rate. The liver injuries of rats induced by the treatment of carbon tetrachloride or ethanol were manifested by the observation of the significant changes in liver weight, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, serum thiobarbituric acid reactive substances (TBARS), and microsomal detocification enzymes(cytochrome P_450), cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase).The effect of PBF on the liver damage induced by the chemicals was evaluated with the extent modulated in change of biochemical parameters above. Exposure to ethanol alone resulted a significant change in the ration of liver per body weight, ALT activity, and microsomal detoxification enzymes (cytochrome P_450, cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase), but did not significantly changes in the levels of serum AST activity and TBARS. Pretreatment coith PBE did not modulate the alteration of the ratio of liver to body weigth, and the activities of serum aminotransferascs (AST. ALT), TBARS, and micro somal detoxification enzyme (cytochrome p_450, cytochrome b$_{5}$,and cytochrome b$_{5}$ reductase. These result suggested that PBE has not appreciable therapeutic effect on carbon tetrachloride or ethanol induced hepatotoxicity.

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Effects of Danggwisayeok-tang (Dangguisinitang) on MIA-Induced Osteoarthritis Rats (당귀사역탕(當歸四逆湯)이 MIA로 유발된 골관절염 흰쥐에 미치는 영향)

  • Yang, Doo-Hwa;Woo, Chang-Hoon;Kim, Jung-Min;An, Hee-Duk
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.2
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    • pp.37-50
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    • 2015
  • Objectives The purpose of this study was to know the effects of Danggwisayeok-tang (Dangguisinitang) extract (DGSYT) on monosodium iodoacetate (MIA)-induced rat osteoarthritis. Methods For this purpose, rats were divided into 5 groups. Normal group was not injected with MIA and orally administered any medication. Control group was injected with MIA and not orally administered any medication. DGSYT100 group was injected with MIA and orally administered 100 mg/kg of DGSYT. DGSYT300 group was injected with MIA and orally administered 300 mg/kg of DGSYT. JoinsT group was injected with MIA and orally administered 20 mg/kg of Joins tablet. DGSYT100 and DGSYT300 groups were orally administered DGSYT during a week before and 3 weeks after based on the day MIA injected. The changes of hepatotoxicity, nephrotoxicity, relative hind paw weight distribution, cytokine in serum, cytokine messenger ribonucleic acid (mRNA) in joint tissue and histopathological observation (Hematoxylin & Eosin and Safranin-O staining) were measured. Results Alanine aminotransferase (ALT) levels of DGSYT100, DGSYT300 and JoinsT groups were increased significantly, but these results were within normal range. Aspartate aminotransferase (AST) and creatinine levels of all groups were not changed significantly. In the change of relative hind paw weight distribution, DGSYT300 and JoinsT groups were decreased significantly 14 and 21 days after MIA injected. Interleukin-$1{\beta}$ (IL-$1{\beta}$) and Interleukin-6 (IL-6), Leukotriene $B_4$ and Osteocalcin levels of DGSYT300 and JoinsT groups were decreased significantly. In measurement of IL-$1{\beta}$ and nitric oxide synthase-II mRNA relative quantitative of control, DGSYT100, DGSYT300 and JoinsT groups were decreased significantly. In measurement of TNF-${\alpha}$, IL-6 and Cyclooxygenase-2 mRNA relative quantitative of control, DGSYT300 and JoinsT groups was decreased significantly. In histopathological observation of knee, synovial tissue, cartilage and proteoglycan of DGSYT100, DGSYT300 and JoinsT were well preserved compared with control group. Conclusions According to the results, DGSYT has anti-inflammation and pain relief effects. So it should be suppressed progression of arthritis in MIA-induced osteoarthritis rat.

A Case of Imatinib-mesylate associated Hypersensitivity Pneumonitis (Imatinib-mesylate에 의한 과민성 폐렴 1예)

  • Lee, Jae Wong;Kim, Hye Jin;Kim, Kyu Jin;Shin, Kyeong Cheol;Hong, Yeong Hoon;Chung, Jin Hong;Lee, Kwan Ho
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.4
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    • pp.423-426
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    • 2005
  • Imatinib-mesylate (Gleevec, Glivec) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib is also used to treat patients with c-kit (CD 117)-positive unresectable tumors, or metastatic malignant gastrointestinal stromal tumors, or both. Imatinib is a welltolerated drug with few side effects. However, it has been associated with gastrointestinal irritation, fluid retention and edema, skin rashes, depigmentation, hepatotoxicity, hemorrhage, and hematological toxicity (anemia, neutropenia, and thrombocytopenia). In addition, imatinib has been associated with dyspnea and cough, which are mainly secondary to the pleural effusion and pulmonary edema, which represent local or general fluid retention. These events appear to be dose related and are more common encountered in the elderly. However, there has been no report of hypersensitivity pneumonitis associated with imatinib-mesylate in Korea. We report a case of 51-year old woman who developed hypersensitivity pneumonitis that might have been induced by imatinib-mesylate during the treatment of a gastrointestinal stromal tumor.

The Anti-Fibrogenic Effect of a Pharmaceutical Composition of[5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (Oltipraz) and Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB)

  • Kang, Keon-Wook;Kim, Yoon-Gyoon;Kim, Choon-Won;Kim, Sang-Geon
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.655-663
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    • 2002
  • Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

Effect of Ramaria botrytis Methanol Extract on Hepatotoxicity in Benzo(α) Pyrene-treated Mice and Expression of Cytochrome P-450 1A1 Isozyme (벤조피렌 유발 마우스에서 싸리버섯 메탄올 추출물의 간 독성 억제효과 및 사이토크롬 P-450 1A1 Isozyme의 발현에 미치는 영향)

  • Kim, Hyun-Jeong;Lee, In-Seon;Bae, Jun-Tae;Kim, Ok-Mi;Park, Sun-Hee;Chang, Jong-Sun;Park, Jun-Hong;Lee, Kap-Rang
    • The Korean Journal of Mycology
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    • v.31 no.1
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    • pp.34-39
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    • 2003
  • This study was conducted to investigate effects of Ramaria botrytis methanol extract on liver damage in benzo$({\alpha})$pyrene(B$({\alpha})$P)-treated mice. The activities of serum amminotransferase, cytochrome P-450, aminopyrine N-demethylase, aniline hydroxylase and hepatic content of lipid peroxide after B$({\alpha})$P-treatment were increased than control, but those levels were significantly decreased by the treatment of Ramaria botrytis methanol extract. Whereas, the hepatic glutathione content and activities of glutathionie S-transferase and r-glutamylcysteine syntherase were increased by the treatment of Ramaria botrytis methanol extract. In addition, cytochrome P-450 1A1 izozyme protein level, remarkably increased by B$({\alpha})$P-treatment was decreased by the treatment with methanol extract of Ramaria botrytis. These results suggest that the protective effect of methanol extract of Ramaria botrytis on liver injury in B$({\alpha})$P-treated mice may be due to reduction of oxygen free radical.

Protective effects of dandelion extract against liver damage by repeated administration of thioacetamide in rats (랫드에서 thioacetamide의 반복 투여로 유도된 간 손상에 대한 민들레 추출물의 효과)

  • Moon, Sun-Jin;Shin, Sung-Shik;Son, Chang-Ho;Oh, Ki-Seok;Kim, Ha-Jung;Jung, Ji-Young;Suh, Guk-Hyun
    • Korean Journal of Veterinary Service
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    • v.40 no.2
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    • pp.107-117
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    • 2017
  • This study was conducted to investigate of hepatoprotective effect of dandelion water extract (DWE) according to repeated administration of thioacetamide (TAA) induced hepatotoxicity in Spraque-Dawley rats. Thirty rats were randomly assigned to 5 groups; normal control, DWE-control, TAA-control (TAA injection during the feeding of normal diet), TAA&DWE600 (TAA repeated injection during the feeding of DWE 600 mg/kg BW), TAA&DWE1200 (TAA repeated injection during the feeding of DWE 1,200 mg/kg BW). Rats in DWE-control and TAA&DWE groups were treated with DWE (600 or 1,200 mg/kg BW daily) by gavage for 20 days (twice a day). All the rats in the TAA-control and TAA&DWE groups were repeated injection of TAA (100 mg/kg BW) into the abdominal cavity 3 days interval and 12 hrs later, all rats were sacrificed. At the same time, normal control and DWE-control groups were injected normal saline. In TAA&DWE groups, serum alanine and aspartate aminotransferase (ALT, AST) were significantly decreased and triglyceride (TG) synthesis was significantly increased compared to TAA group. As well as total billilubin and GGT were slightly decreased by the treatment of DWE. Lipid peroxidation (MDA) concentration was significantly decreased and hepatic GSH content was slightly or significantly increased in the TAA&DWE groups compared to TAA group. Hepatic anti-oxidative enzyme activities, such as GSH, GST, SOD and catalase were slightly or significantly elevated by the treatment of DWE. According to these results, When dandelion extract was long term supplied, it could be used as a potential protective material for a longer time liver damage by repeated adminstration of the TAA.