• Title/Summary/Keyword: $CCl_4$-induced liver damage

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Protective effects of EDTA and EGTA against CCl4-induced acute hepatotoxicity in mice (마우스에서 사염화탄소로 유발된 급성 간독성에 대한 EDTA 및 EGTA의 보호효과)

  • Park, Seung-Guk;Cho, Yong-Do;Shin, Taekyun;Wie, Myung-Bok
    • Korean Journal of Veterinary Research
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    • v.47 no.3
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    • pp.265-271
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    • 2007
  • This study investigated the protective effects of ethylene glycol-bis(${\beta}$-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), an extracellular calcium chelator, and ethylenediaminetetraacetic acid (EDTA), which chelates calcium and most metal ions, against carbon tetrachloride ($CCl_4$)-induced acute hepatotoxicity in mice. Mice were treated with EGTA or EDTA at a dose of 20 (low) or 100 mg/kg (high) subcutaneously 1h before $CCl_4$ administration. The mice were fasted and sacrificed 18h after $CCl_4$ treatment. Blood samples were collected from the carotid artery by decapitation under light ether anesthesia. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and cholesterol levels were measured. Malondialdehyde (MDA) production was determined as an index of lipid peroxidation in the liver. The liver, kidneys, and spleen were weighed. We also evaluated the histopathological changes in the liver in each group. The relative weights of the liver were significantly higher in the $CCl_4$-treatment group than in the normal group, except in the high-EDTA treatment group. EGTA and EDTA treatment caused a significant decrease in serum ALP, ALT, and AST levels. Of all of the doses of EGTA and EDTA tested, the high-EDTA dose resulted in the most remarkable inhibitory action. The protective effect in the high-EDTA-treatment group was confirmed histopathologically. The low-EGTA-treatment group showed a significant decrease in serum TG and cholesterol levels. Liver MDA levels were significantly decreased in the EGTA (20 mg/kg) and EDTA (20, 100 mg/kg) groups. These results suggest that EDTA, which chelates both calcium and metal ions, confers better protection in $CCl_4$-induced acute liver damage than does EGTA, a calcium chelator.

Synergetic Hepatoprotective Effects of Korean Red Ginseng and Pueraria Radix on the Liver Damaged-Induced by Carbon Tetrachloride (CCl4) in Mice

  • Hwang, Seung Hwan;Wang, Zhiqiang;Kang, Il-Jun;Lim, Soon Sung
    • Natural Product Sciences
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    • v.23 no.2
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    • pp.132-138
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    • 2017
  • This study was designed to investigate the synergetic hepatoprotective effects from a mixture of Korean Red Ginseng and Pueraria Radix on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in mice. Liver toxicity was induced by intraperitoneal administration of $CCl_4$ (0.6 mg/kg) in 12 groups of ICR mice. The negative control group was given $CCl_4$ without test samples and the normal group was given no treatment. Among treatment groups, the RGAP treatment (Korean Red ginseng acetic acid extract : Pueraria radix water extract, w/w, 38.4:57.6) decreased $CCl_4$-elevated ALT (101.60 IU/L), AST (833.89 IU/L), and LDH (365.02 IU/L) levels in the serum, and increased the SOD (11.03 unit/mg protein) and CAT (0.37 unit/mg protein) levels and the LPO levels ($59.09{\mu}M/g$ tissue) more than that in the mice group with $CCl_4$-induced control group hepatotoxicity. These results suggest that administration of a mixture of Korean Red ginseng and Pueraria radix decreases $CCl_4$-induced liver damage and enhances antioxidant activity in mice and imply that administration of the mixture in a certain ratio is more effective than single administration of either Korean Red ginseng or Pueraria radix alone.

Effects of Mori Folium and Crataegus pinnatifida Leave Extracts on $CC1_4$-induced Hepatotoxicity in Rats (상엽과 산사엽 추출물이 사염화 탄소로 유발된 흰쥐의 간 손상에 미치는 영향)

  • 김형진;김중권;황완균;함인혜;권석형;황보식;김홍진
    • YAKHAK HOEJI
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    • v.47 no.4
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    • pp.206-211
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    • 2003
  • This study was performed to investigate the effect of Mori Folium and Crataegus pinnatifida leave extracts on liver damage induced by CC1$_4$ in rats. 30% and 60% methanol extracts of Mori Folium and Crataegus pinnatifida leaves were administered orally at the dose of 10 mg/kg on every day for 6 days and liver damage was induced by intraperitoneal injection of $CCl_4$ (0.4 ml/kg) on 6th day. 30% Methanol extracts of Mori Folium treated group showed significant protective effect on hepatotoxicity with the lowest Glutamic Oxaloacetic Transaminase (GOT) and Glutamic Pyruvic Transaminase (GPT). The low density lipoprotein (LDL) levels of 30% methanol extracts of Mori Folium and Crataegus pinnatifida leave and 60% methanol extracts of Mori Folium treated groups were significantly lower than normal group, respectively. In particular, LDL level of 30% Mori Folium extracts treated group was significantly decreased compared to $CCl_4$ treated group. These results support that Mori Folium and Crataegus pinnatifida leave extracts are hepatoprotective effects against hepatotoxicity induced by $CCl_4$.

Protective Effect of 6 Food Mixed-Extract on the CCl4-Induced Hepatic Damage in Rats (6종 식품의 혼합추출물이 사염화탄소로 유도된 흰쥐 간 손상에 미치는 보호효과)

  • Hwangbo, Mi-Hyang;Yea, Chun-Jung
    • The Korean Journal of Food And Nutrition
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    • v.31 no.6
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    • pp.828-835
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    • 2018
  • The objective of this study was to examine the biochemical parameters of hepatic function such as serum level of ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase), LDH (lactate dehydrogenase), and content of TG (triglyceride) and cholesterol, and tissue immunological changes of the $CCl_4$-treated rats with administration of the mixed sample extract (MSE). The liver weight in $CCl_4$-administered experimental control group (EC) was slightly higher than that of normal control (NC) group. Hepatic damage parameters (ALT, AST, ALP, LDH & TG) in serum of the EC group were significantly higher than those in serum of the NC and silymarin-treated positive control (PC) group. On the other hand, these hepatic damage parameters of MSE-treated experimental (E1 & E2) groups were significantly lower than those of EC group. The number of WBC, neutrophils, lymphocytes and platelets, and the contents of hemoglobin, and hematocrit in EC group were significantly higher than those of NC group. However, the number of WBC and lymphocytes in E1 and E2 groups were significantly lower than those of EC group. Also, the collagen developmental areas in the liver of NC and PC groups by hepatic immuno-histological findings were found slightly positive. Whereas, hepatic fibrous developmental tissue of EC group was strongly positive brown color band, those of E1 & E2 groups were decreased. Therefore, it was concluded that the induction of hepatic fibrous tissue activation had a preventive effect of MSE against the $CCl_4$-induced hepatic damage in rats. However, further study is needed in this filed.

Methanol Extract of Agaricus blazei Murill Reduces Hepatic Damage Induced by $CCl_4$ and High Fat and Improves Liver Lipid Profile in Rats

  • Jung, Myung-Eun;Kwon, Hyuck-Se;Shin, Se-Gye;Jin, Yong-Xie;Han, Eun-Kyung;Ham, Seung-Shi;Kang, Il-Jun;Chung, Cha-Kwon
    • Nutritional Sciences
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    • v.9 no.4
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    • pp.267-272
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    • 2006
  • The effect of methanol extract from Agaricus blazei Murill on the hepatotoxicity was investigated $CCl_4$ is one of the oldest and most widely used toxins for the induction of hepatic damages and fibrosis in experimental animals. In this study, male Sprague-Dawley(SD) rats were randomly divided into 6 groups of the control(C), $CCl_4(T),\;CCl_4$ and high fat group(TL) with matching sub-groups of Agaricus blazei Murill extract-fed groups of CA, TA and TLA. Methanol extracts of Agaricus blazei Murill were fed 50 mg/kg B.W daily via drinking water. A 1.2 mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total of six times. The levels of total-cholesterol, TG, LDL and LDL-phospholipids were elevated by $CCl_4$ treatment as compared to the control(C). However, Agaricus blazei Murill methanol extract feeding in the group of TA and TLA significantly(p<0.05) decreased TG by 53.1 % and 17.9% compared to the internal control of T and TL, respectively. Triglyceride of TL was increased by 3.33 times(p<0.05) compared to the control(C) with $CCl_4$ and high fat administration from 3.78 mg/g to 12.60 mg/g liver. The extract(CA) also reduced kidney weight compared to the control(C). With the administration of high fat and $CCl_4$(TLA), the extract reduced the organ weight of both liver and kidney and further, significantly reduced TG, total cholesterol and GTP activity. Hepatoprotective effects of Agaricus blazei Murill on GOT, GPT, AP and LDH activities were enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract reconstituted the damaged cytoplasm and stimulated mitochondriogenesis. The above results suggest that Agaricus blazei Murill may have a possible protective effect against chemically induced liver damage and further help to reduce the symptoms of fatty liver.

Effect of Solanum lyratum Extract on the Hepatotoxicity of Carbon Tetrachloride in Rats (백모등 엑스의 간기능개선 효과)

  • Yang, Jae-Heon;Choi, Cheol-Ung;Kim, Dae-Keun;Lee, Kang-Ro;Zee, Ok-Pyo
    • Korean Journal of Pharmacognosy
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    • v.27 no.3
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    • pp.167-172
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    • 1996
  • The studies were attempted to investigate the therapeutic effect of Solanum lyratum extract(SLE) on the liver damage induced by carbon tetrachloride in rats. Male rats (Sprangue-Dawley) were treated with subchronic concentration of $CCl_4$, which was 1 mg/kg of $CCl_4$ via per oral administration daily for three days. The level of serum cholesterol, transaminase, bilirubin and BSP were measured. Treatment of SLE significantly decreased the increment in serum transaminase activities, total cholesterol and enlargement of liver but serum bilirubin was not reduced. The protective effect was observed when SLE was given daily for 4 weeks after $CCl_4$ treated for 3 days. SLE administration to rats prevented the development of fatty change, necrosis, and fibrosis induced by $CCl_4$. The results suggest that SLE has appreciable therapeutic effect on $CCl_4$ induced hepatotoxicity.

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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.

Liver-protective Activities of Alisol Compounds against $CCl_4$ Intoxication (택사(澤瀉)로부터 분리(分離)한 Alisol 성분(成分)의 간(肝) 보호작용(保護作用))

  • Chang, Il-Moo;Kim, Young-Soo;Yun, Hye-Sook;Kim, Sun-Ok
    • Korean Journal of Pharmacognosy
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    • v.13 no.3
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    • pp.112-115
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    • 1982
  • Alisol A monoacetate, alisol B monoacetate, alisol C monoacetate and alisol B were isolated from Alismatis Rhizoma, which is a herbal drug used frequently in the oriental prescriptions. Potential liver-protective activities of the isolated alisol compounds were evaluated against $CCl_4-induced$ liver damage. The results obtained from liver microsomal enzyme assay, measurement of serum glutamic pyruvic transaminase (EC 2.6.1.2) and serum triglyceride content indicated that alisol A,B and C monoacetates showed significant liver-protective activities against $CCl_4$ poisoning. Alisol B monoacetate exhibited slightly higher activity than that of alisol B.

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Immunoregulatory Effects of Water Extracts of Inonotus obliquus in Carbon Tetrachloride-Induced Liver Damage Animal Model (사염화탄소로 유도된 간 손상 동물모델에서 차가버섯 열수 추출물이 면역 조절 기능에 미치는 영향)

  • An, Chi-Sun;Jin, Hai-Lan;Jeon, Yun-Hui;Bak, Jong-Phil;Kim, Jong-Dai;Yoon, Jung-Han;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.18 no.1
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    • pp.1-8
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    • 2010
  • Inonotus obliquus is one of the immune-regulatory substances and is recognized to play the role in the metabolic process of inflammation, allergy and immuntiy. The purpose of this study was to evaluate the effects of water extracts of Inonotus obliquus (IOW) on the liver lymphocyte immune function in the Sprague-Dawley male rats treated with carbon tetrachloride ($CCl_4$) to induce liver damage. Rats were fed with each experimental diet and water for 4 weeks. We found that effects of IOW on interferon-gamma (IFN-$\gamma$), signal transducer and activator of transcription 1 (STAT1), phospho-signal transducer and activator of transcription 1 (pSTAT1) and GATA-binding protein 3 (GATA-3) were decrease in vivo. Interleukin-4 (IL-4), STAT6, pSTAT6 and T-box expressed in T-cells (T-bet) decreased significantly lower in $CCl_4$+IOW group than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group and $CCl_4$+IOW group. As a result of this study, we assume that IOW fed could regulate the immuno-modulating functions through regulate the cytokine production capacity activated by liver damage.

Protective Effects of Gami Yugan-tang on Liver Damage in Rats (흰쥐의 간손상(肝損傷)에 대한 가미유간탕(加味愈肝湯)의 간(肝) 보호효과(保護效果))

  • Jung, Hee;Go, Ho-Yeon;Hsia, Yu-Chun;Yeo, Hyun-Soo;Baik, Jong-Woo;Ko, Seung-Gyu;Park, Jong-Hyung;Jun, Chan-Yong;Kang, Jea-Chun
    • The Journal of Internal Korean Medicine
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    • v.29 no.1
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    • pp.265-277
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    • 2008
  • In order to investigate the protective effects of Gami Yugan-tang on liver damage in rats induced by $CCl_{4}$ and d-galactosamine, the serum transaminase(ALT & AST), alkaline phosphatase(ALP), lactic dehydrogenase(LDH), superoxide dismutase(SOD), catalase, glutathione S-transferase(GST), glutathione peroxidase(GPX) for enzyme activities, and lipid peroxidation were measured. All animals were divided into 4 groups: normal group (untreated), control group (treated with 0.9% saline solution), sample I group (treated with 740mg/kg Gami Yugan-tang), and sample II group (treated with 1,480mg/kg Gami Yugan-tang). The results were as follows : 1. The results of liver damage in rats induced by $CCl_4$ : The protective effects of ALT were displayed in sample I and sample II, and AST, ALP, LDH, SOD, catalase, GST, GPX, and lipid peroxidation were noted in sample II group. It showed slight necrosis of hepatic cell and pathologic changes, for example, inflammatory cells infiltration were improved in sample II group compared to the control group. 2. The results of liver damage in rats induced by d-galactosamine : The inhibitory effects of AST, ALT, LDH, and ALP activities were noted in both sample I and sample II groups. The findings from this experiment suggests that Gami Yugan-tang has protective effects against liver damage in rats induced by $CCl_{4}$ and d-galactosamine.

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