• Title/Summary/Keyword: $CCl_4$ administration

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Improvement of Liver Function and Suppressed Lipid Peroxidation of Extract from Ginseng Folium and Stem in Acute $CCl_4$ Intoxicated Rats ($CCl_4$로 급성 간손상을 유도한 백서에서 인삼엽과 경추출물의 간기능 개선과 항산화 작용)

  • Lee Min Kyung;Park Sung Hye;Seo Eui Suok;Kim Ki Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.5
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    • pp.1485-1489
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    • 2004
  • Panax ginseng is the one of best famous phytochemical plant in the world and it's various positive effects such as antioxidant, regulation of immunity are very well known. In this study, we investigated primary the cell viability and morphological change and secondary an antioxidative effect and liver function improvement of extract from Ginseng folium and stem in CCl4 intoxicated rats. The NCTC cell line were used for cell viability and sirius red staining before the animal experiment. The female Sprague-Dawley rats (90-100g) were divided into 3 groups (Normal, AC: CCl₄ treated group, GFS: CCl₄+ extract of Ginseng folium and stem treated group) and acute liver damage was developed by one time administration of CCl₄ mixture (0.5㎖/rat). The liver tissue and sera were collected and used for quantitative measurement of enzyme activity (AST, ALT, ALP, BUN), MDA and Hyp. As a result, cell viability in GFS treated group (in concentration of 3.33-33.33㎎ GFS/200㎕ medium) was 180.9-241.0% significantly and dose dependently higher than in control group. And potential state of cell growth and differentiation and no criteria of cytoplasm lysis and nucleus breaking were observed in control and GFS group. The parameters of liver function (AST and ALP) in sera of GFS group showed significantly 93% and 67.6% lower than AC group (p<0.005-0.05). And the level of ALT and BUN showed fast similar in AC group and GFS group. The concentration of MDA in liver was decreased 576.5% significantly in GFS group when compared with AC group (p<0.005). The content of Hyp in GFS group is merely lower than in AC group. In conclusion, the water extract of Ginseng folium and stem such as Ginseng radix may be possessed the antioxidative effect and improvement of liver function in CCl₄ intoxicated rats.

Hepatic Gene Expression Analysis of Gadolinium Chloride Treated Mice

  • Jeong, Sun-Young;Lim, Jung-Sun;Hwang, Ji-Yoon;Kim, Yong-Bum;Kim, Chul-Tae;Lee, Nam-Seob;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.2 no.1
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    • pp.21-28
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    • 2006
  • Gadolinium chloride ($GdCl_{3}$) was known to block Kupffer cells and generally its toxicity study based on blocking these cells. Therefore, $GdCl_{3}$ frequently used to study toxic mechanisms of hepatotoxicants inducing injury through Kupffer cells. We also tried to investigate the effect of $GdCl_{3}\;on\;CCl_{4}$ toxicity, typical hepatotoxicants. Administration of $GdCl_{3}$ to mice significantly suppressed AST (asparatate amino transferase), ALT (alanine amino transferase) levels which were increased by $CCl_{4}$ treatment. However, $GdCl_{3}$ didn't inhibit the phagocytotic activity of Kupffer cells. Malondialdehyde (MDA) is a good indicator of the degree of lipid peroxidation. In this study, MDA increased by $GdCl_{3}$ administration not by $CCl_{4}$. To understand the toxicity of $GdCl_{3}$, we analyzed global gene expression profile of mice liver after acute $GdCl_{3}$ injection. Four hundred fifty two genes were differentially expressed with more than 2-fold in at least one time point among 3 hr, 6 hr, and 24 hr. Several genes involved in fibrogenesis regulation. Several types of pro-collagens (Col1a2, Col5a2, Col6a3, and Col13a1) and tissue inhibitor of metal-loproteinase1 (TIMP1) were up regulated during all the time points. Genes related to growth factors, chemokines, and oxidative stress, which were known to control fibrogenesis, were significantly changed. In addition, $GdCl_{3}$ induced abnormal regulation between lipid synthesis and degradation related genes. These data will provide the information about influence of $GdCl_{3}$ to hepatotoxicity.

Toxicogenomics Study on Carbon Tetrachloride-induced Hepatotoxicity in Mice

  • Jeong, Sun-Young;Lim, Jung-Sun;Hwang, Ji-Yoon;Park, Han-Jin;Cho, Jae-Woo;Song, Chang-Woo;Kim, Yang-Seok;Lee, Wan-Seon;Moon, Jin-Hee;Han, Sang-Seop;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.275-280
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    • 2005
  • Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

Hepatoprotective Effect of Cheonnyuncho (Opuntia humifusa) Extract in Rats Treated Carbon Tetrachloride (천년초(Opuntia humifusa) 추물물의 사염화탄소를 처치한 흰쥐에서의 간보호 효과)

  • Park, Min-Kyung;Lee, Young-Jae;Kang, Eun-Sil
    • Korean Journal of Food Science and Technology
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    • v.37 no.5
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    • pp.822-826
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    • 2005
  • Effect of Cheonnyuncho extract on the liver injury of rats treated carbon tetrachloride $(CCl_4)$ was studied. Cheonnyuncho extract was administerd at dose of 0.5 and 1 g/kg/day, p.o. for 2 weeks. $CCl_4$ was treated at dose of $0.5\;mL/kg$, i.p. 3 hours later from the last pretreatment of Cheonnyuncho extract. Administration of Cheonnyuncho extract at a dose of 1 g/kg decreased serum AST, ALT and ALP activities by 36, 41, and 22% respectively compared to $CCl_4$ treatment group. Increased lipid peroxidation and decreased SOD and GST activities were also recovered by pretreatment of Chonnyuncho extract in liver of rats. These results suggest that Cheonnyuncho extract has hepatoprotective effect against liver injury.

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.

Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride (알코올 및 사염화탄소에 의해 유발된 급만성 간손상에 대한 지구자 열수추출물의 보호효과)

  • Kim, Young-Sik;Park, Juyeon;Kwon, Yongbeom;Lim, Dong Wook;Song, MiKyung;Choi, Ho-Young;Kim, Hocheol
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.25-32
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    • 2013
  • Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and $CCl_4$ in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute $CCl_4$-induced liver injury, rats received a single dose of $CCl_4$ (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after $CCl_4$ administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and ${\gamma}$-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and ${\gamma}$-GTP levels compared to control group. In acute $CCl_4$-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute $CCl_4$-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.

Study on Atractylodes Rhizomes( II ) : Liver-Protective Activites of Atractylodes Rhizome and Atractylodes Rhizome White(Old and Newly-Grown Rhizomes of A. japonica Koidz.) in Mice (출류(朮類)에 관한 연구( II ) : 한국산(韓國産) 창출(蒼朮)과 백출(白朮)의 사염화탄소 간독성(肝毒性)에 대한 보간효과(補肝效果) 비교(比較))

  • Chang, Il-Moo;Mar, Woong-Chon;Kim, Jae-Hoon;Yeom, Jeong-Rok;Takido, Michio
    • Korean Journal of Pharmacognosy
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    • v.20 no.2
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    • pp.96-100
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    • 1989
  • Traditional herbal drugs of Korea, namely, Atractylodes Rhizome(蒼朮) and Atractylodes Rhizome White(白朮) which are derived from and old-grown rhizome and a newly-grown rhizome of Atractylodes japonica Koidz.(Compositae), respectively, were investigated their potential liver-protective activities against hepatotoxicity induced by $CCl_4$ intoxication in mice. Each herbal drug was extracted separately with chloroform, methanol and butanol. No extract of Atractylodes Rhizome showed a significant reduction of the duration of hypnosis produced by hexobarital after $CCl_4$ intoxication in mice. In addition, the the treatments of Atractylodes Rhizome extracts produced no decrease of aspartate aminotransferase(EC 2.6.1.1) activity in serum. However, the methanol extract of Atractylodes Rhizome White exhibited a marked protection from hepatotoxicity induced by $CCl_4$ intoxication in mice. It produced significant reductions of the duration of hypnosis and serum enzyme activity, but no other extract showed liver-protective activity against $CCl_4-induced$ hepatotoxicity.

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Effects of Callophyllis japonica powder on carbon tetrachloride-induced liver injury in rats

  • Park, Dal-Soo;Lee, Ki-Hyun;Kim, Hee-Chul;Ahn, Mee-Jung;Moon, Chang-Jong;Ko, Myung-Soon;Lee, Kyoung-Kap;Go, Gyung-Min;Shin, Tae-Kyun
    • Advances in Traditional Medicine
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    • v.5 no.3
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    • pp.231-235
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    • 2005
  • A limited number of studies have been conducted on the bioactivity of Callophyllis japonica (C. japonica), which is a red seaweed that is traditional in the oriental diet. In this report, the hepatoprotective effect of C. japonica was studied in a carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity model in rats. A single intraperitoneal injection of 1.25 ml/kg of 20% $CCl_4$ in olive oil produced an elevated level of serum glutamic pyruvic transaminase (SGPT) and increased enzyme activity of serum glutamic oxaloacetic transaminase (SGOT). Pre-treatment with C. japonica (150 mg/kg/d) for 3 days in $CCl_4-injected$ rats reduced the levels of SGPT and SGOT compared with control levels (P < 0.05), while higher doses (300 and 600 mg/kg) were ineffective. The administration of C. japonica (150 mg/kg/d) for 3 days after the $CCl_4$ injection in rats was ineffective at reducing SGPT and SGOT. The histopathological findings in each group largely agreed with the biochemical data. The results of this study support the suggestion that C. japonica has a hepatoprotective effect on chemical-induced liver injury.

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.

Indocyanine green excretion test and changes of plasma enzyme activites in dogs (개에서의 indocyanine green 배설시험 및 혈장효소 활성치의 변화)

  • Kim, Cheol-ho;Choi, Il-kwan;Son, Min-soo;Kim, Jin-gu;Kang, Chung-boo
    • Korean Journal of Veterinary Research
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    • v.32 no.4
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    • pp.671-675
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    • 1992
  • This experiment was carried out to establish a proper method of indocyanine green(ICG) excretion test for a applicable liver function test in dogs. The half life(T1/2), fractional clearance rate(KICG) and retention rate after injection of ICG with or without administred carbon tetrachloride($CCl_4$) were also invested. The results obtained were as follows ; 1. The maximum absorbance of ICG in plasma was at 810nm. 2. Half life and fractional clearance rate when administered 0.25 and 0.50mg of ICG per Kilogram body weight were $6.33{\pm}0.58$ minutes and $0.11{\pm}0.99$/minute in the former, $10.01{\pm}1.0$ minutes and $0.07{\pm}0.007$/minute in the latter, respectively. The ICG removal rate was exponentially linear for the first 15 minutes after injection both, of 0.25 and 0.50mg of ICG. 3. One day following the administration of $0.0042m{\ell}\;CCl_4$ kilogram body weight which injected 0.50mg of ICG, half life was more longer and fractional clearance rate was significantly reduced than that of ICG single injection. 4. Plasma retention rate when 15, 30, 45 minutes after injection dose of 0.25 and 0.50mg ICG per Kilogram body weight, $14.7{\pm}4.8$, $5.1{\pm}3.1$, $2.6{\pm}1.6%$ in the former, $26.9{\pm}1.8$, $11.1{\pm}2.4$, $4.8{\pm}1.3%$ in the latter, respectively. However, after administration of $CCl_4$, plasma retention rate of ICG at a dose of 0.50mg, it was $39.3{\pm}0.9$, $16{\pm}2.9$, $10.7{\pm}0.1%$, respectively. 5. Plasma enzyme(AST, ALT, r-GTP) activities administered with $CCl_4$ were increased, but there was no change which injected any dose of single ICG injection. From these results, ICG excretion test to dog is applicable to evaluation of liver function in both clinical and research.

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