• Title/Summary/Keyword: carbon tetrachloride(CCl4)-induced hepatotoxicity

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A Study of the Histological Effects of Garlic Extract in a Liver-damage Rat Model (마늘 추출물이 간 손상 랫드의 조직학적 변화에 미치는 효과 연구)

  • Lee, Tae-Jong;Min, Kyung-Jin
    • Journal of Environmental Health Sciences
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    • v.36 no.4
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    • pp.279-287
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    • 2010
  • In this study we examined the effects of water extract of garlic on carbon tetrachloride-induced liver injury, and demonstrated increased beneficial enzyme and anti-oxidant activity as well as histopathological changes (by Hematoxylin-Eosin (H&E) staining, Trichrome staining, and TEM examination), and showed that the treatment was dose-dependent and safe. A total of 42 male Sprague-Dawley rats were divided equally (n=7) into six groups. To induce hepatotoxicity in these subjects, carbon tetrachloride diluted in an equal volume of olive oil was intraperitoneally administrated at 0.5 ml/kg (0.20 g/kg/day) once a day for five days. Water extract of Korean-grown garlic was administered via a stomach sonde once a day, 5 days a week, for a total of 4 weeks. Groups received 0.35 g/kg (E1), 0.70 g/kg (E2), or 1.40 g/kg (E3), with the dose adjusted for body weight. Administration of garlic extract resulted in positive physiological effects in terms of reduced oxidative stress and toxicity, and induced functional changes in the liver. Comparing the subject groups (E1, E2, E3) administered different doses of garlic extract, the importance of morphological analysis in further studies is emphasized, because morphological changes indicating hepatotoxicity could occur, even though beneficial enzyme activities were found to be elevated.

Protective effect of STAR of STAR series on CCl4 induced acute hepatotoxicity by regulation of reactive oxygen species (활성산소종의 조절을 통한 음료 '별의별간'의 급성간독성 보호효과)

  • Chang, Bo Yoon;Oh, Jun Seok;Han, Ji Hye;Kim, Da Eun;Hong, Jae Heoi;Kim, Sung Yeon
    • Food Science and Preservation
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    • v.23 no.2
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    • pp.275-282
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    • 2016
  • STAR of STAR (SS 01-04) is a series of drinks that consist of various extracts obtained from Coriolus versicolor, Artemisia capillaris Thunb., Hovenia dulcis, Acanthopanax sessiliflorus, Lycium chinense, Citrus reticulata, Saururus chinensis, Pueraria lobata, Pyrus pyrifolia, and Oenanthe javanica. A purpose of this study was to investigate the hepatoprotective effect of SS 01-04. Antioxidant activity of the drinks was evaluated by conducting a hydroxyl radical-scavenging assay. Cytotoxicity and hepatoprotective potential were determined using HepG2 cells in vitro, while protective effects against acute hepatotoxicity was evaluated in vivo. The antioxidant activity of the SS 01-04 at concentration of 100 and 250 mg/mL was similar to that of $50{\mu}M$ vitamin C. tert-Butyl hydroperoxide (tBHP)-induced production of reactive oxygen species (ROS) was blocked by SS 01, 03 and 04 in a dose-dependent manner. Treatment with SS 04 significantly lowered the serum levels of alanine aminotransferase and aspartate aminotransferase in an animal model of carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity (p<0.05). In addition, SS04 increased glutathione level while decreased malondialdehyde level in the liver considerably (p<0.05). It also inhibited the $CCl_4-induced$ increase in the levels of triglyceride and cholesterol in serum and the liver. These findings indicated that SS 01-04 possessed antioxidant activity and protect against ROS. In particular, SS 04 is potentially highly beneficial in treating liver damage as it scavenges reactive free radicals and boosts the endogenous antioxidant system.

Effect of the Oryungsan on the injured liver in CCl4-treated rats (오령산(五?散)이 CCl4 투여(投與)로 인한 흰쥐의 손상간(損傷肝)에 미치는 영향(影響))

  • Kown, Oh Sung;Choi, Hong Sik;Lee, Joon Hee;Kang, Yoon Ho
    • The Journal of Dong Guk Oriental Medicine
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    • v.5
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    • pp.131-147
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    • 1996
  • This study was investigated to define effect of pretreatment of Oryungsan on hepatotoxicity induced by $CCl_4$ in rat. The experimental anmals were divided into normal group, control group, sample group, and sample group were divided sample1, sample2, sample3. Control group were injected diluted carbon tetrachloride and olive oil, $1m{\ell}/kg$ to intraperitoneal after 8th day. Sample group were injected Oryungsan water extracts, $0.33m{\ell}/kg/day$ to intraperitoneal of sample group1, $0.66m{\ell}/kg$ day to sample group2, $1.32m{\ell}/kg/day$ to sample group 3 each other for 7day, and injected the dosage of $CCl_4$ was $1.0m{\ell}/kg$ diluted 1 : 1 with olive oil after 8th day. The following results were made by observation GOT, GPT, Albumin, Globulin, Bile acid, hepatic tissue. 1. The serum GOT and GPT level of sample group were decreased. Sample group 1 were decreased significantly. 2. The serum A/G ratio of sample group was increased as compared with normaI group. 3. The serum bile acid of sample group was decreased significantly. 4. The destruction of hepatic tissue were repaired as compared with control group. These results demonstrated that oryungsan can be attributed to recovery from hepatotoxicity.

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Antioxidant Action of Malotilate on Prolonged Hepatic Injury Induced by Carbon Tetrachloride Alone or in Combination with Ethanol in Rat (사염화탄소 및 에탄올에 의해 유도된 만성간 손상에 미치는 말로틸레이트의 항산화 작용)

  • Kim, Hyoung-Chun;Hur, In-Hoi
    • YAKHAK HOEJI
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    • v.34 no.4
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    • pp.267-276
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    • 1990
  • To achieve a better understanding of antioxidant action manifested by malotilate, the dithiol malonates, we monitored the oxy radical-scavenging system against the chronic hepatic damage induced by $CCl_4$ alone or in combination with ethanol. Malotilate was given orally at a dose of 100 mg/kg/day and $CCl_4$ 1.5 ml/kg was injected subcutaneously twice a week for 4 weeks. In each group receiving ethanol, drinking water was replaced by 20% aqueous solution or glucose, isocaloric amounts of ethanol, as a control of ethanol was diluted in its drinking water. Each rat was killed as a starved state at 18 hours after the period of the experiment, four weeks. The results were summarized as follows: 1) Malotilate inhibited the rate of generation of superoxide radicals, the accumulation of lipoperoxides, and promoted the synthesis of glutathione in the liver. 2) Malotilate stimulated the enhancement of activity of superoxide dismutase in hepatic mitochondria. 3) Malotilate had no effects on the hepatic $H_2O_2$ contents. 4) Malotilate showed the increase of catalase activity in the liver poisoned with $CCl_4$, and also gave a tendency to increase it in the liver intoxicated with ethanol. Thus, our data suggested that the activation of hepatic antioxidant system in the presence of malotilate would play a role in protecting liver against the toxic effects of oxy radical and/or lipid peroxides under the hepatotoxic conditions induced by $CCl_4$ with or without ethanol. However, the effects of malotilate against the ethanol-induced hepatotoxicity appear to be insignificant.

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An isolation of the active component of Carthamus tinctorius L. Semen and the evaluation of its hepato-protective effect

  • Jeong, Jeong-Suk;Jeong, Choon-Sik;Jung, Ki-Hwa
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.179-179
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    • 1998
  • We previously reported the hepato-protective effect of butanol soluble fraction of methanolic extract of Carthamus tinctorius L. Semen on carbon tetrachloride induced hepatotoxicity. In this study, the active component from the butanol soluble fraction was isolated by column chromatographic separation using Silica gel and Sephadex LH -20 and identified by spectroscopic methods such as Mass, $^1$H - NMR and $\^$13/C-NMR. The hepato-protective effect of the isolated active component on the CCl$_4$-induced liver damaged rats has been evaluated by performing blood chemical analysis and biotransformational enzyme analysis.

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Protective Effects of near nile Juice Against Carbon Tetrachloride-Induced Acute Hepatotoxicity in ICR Mice (웅담이 CCl4로 유발된 mouse의 간 손상에 미치는 영향)

  • Kim, Hyun-Do;Lee, Kyu-Jae;Park, Seong-Kyu;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.8 no.3
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    • pp.31-38
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    • 2005
  • Objectives : This study was aimed at investigating liver protection mechanism of bear bile juice (Fel Ursi)by inducing liver toxicity through $CCl_4$ in mice and evaluated histological and serological findings. Methods : Experiment groups was categorized into untreated normal group, $CCl_4$ treated control group, and orally administered bear bile juice experiment group. At the termination of experiment, gross examination of the liver as well as histological findings, and Total protein, Albumin, Total bilirubin, Direct bilirubin SGOT, SGPT, and ALP contents in the serum were evaluated. Results : 1. For gross examination and histological findings, $CCI_4$ treated control group showed destroyed lobular structure, increased fibrosis, as well as hepatic cirrhosis. For the group treated with bear bile juice, the lobular structure suffered less damage, and showed lower level of fibrosis and liver cirrhosis compared to the control group. 2. For serum analysis, Total protein and Albumin were significantly increased in the bear bile juice experiment group than the control group. Total bilirubin and Direct bilirubin didn't show significant differences between the two groups. SOOT, SGPT, and ALP were significantly decreased in the normal and bear bile juice experiment groups compared to the control group. Conclusion : Taken together, bear bile juice can be effectively used for recovering the liver functions and further researches must be conducted to verify the efficacies of bear bile juice.

Hepatoprotective effect of Bifidobacterium adolescentis SPM0212 on carbon tetrachloride induced hepatotoxicity (사염화탄소로 유도된 간 손상에 대한 비피도박테리움 어돌레센티스 SPM0212의 보호효과)

  • Lee, Dokyung;Park, Jaeeun;Kim, Minji;Lee, Youngjoo;Seo, Jaegoo;Ha, Namjoo;Kim, Kyungjae
    • Korean Journal of Microbiology
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    • v.51 no.3
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    • pp.280-287
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    • 2015
  • Probiotics are microbial food supplements or components of bacteria which have traditionally been added to dairy foods for extra health boost. Our aim was to evaluate the hepatoprotective effect of Bifidobacterium adolescentis SPM0212 as probiotics, which we previously found has potential anti-hepatitis B virus activity. The study was conducted using Wistar albino rats and probiotics were treated orally for 9 days consecutively and acute liver injury was induced by administration of carbon tetrachloride ($CCl_4$) on the 7th and 8th days. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT), as well as by histopathological examination. B. adolescentis SPM0212 significantly prevented the elevation of SGOT and SGPT levels, and reduced the negative effect of $CCl_4$ on body and organ weights. Histopathological study revealed the livers of the carbon tetrachloride treated rats showed almost complete loss of normal hepatocyte architecture, but that rats treated with B. adolescentis SPM0212 showed minimal damage and normal hepatocyte architecture. Our results suggest that B. adolescentis SPM0212 be considered useful probiotics for protecting the liver from xenobiotics and hepatitis B virus, and as well as useful as a functional food for maintaining human health.

Effects of Godulbaegi Leaf Extracts on $CCl_4$-Induced Hepatotoxicity in Rats (고들빼기 잎추출물이 흰쥐의 사염화탄소에 의한 간손상에 미치는 영향)

  • 배송자;김남홍;하배진;정복미;노승배
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.1
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    • pp.137-143
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    • 1997
  • This study was carried out to investigate the effect of godulbaegi leaf extracts on detoxication of liver injury in $CCl_4$-treated rats. We divided normal group(5) and $CCl_4$-treated group and then $CCl_4$- treated group was divided into 6 groups; only $CCl_4$-treated group(CS), aqueous extract pretreated group (CSA), n-butanol extract pretreated group(CSB), Tween 80 pretreated group(CT), n-hexane extract pretreated group(CTH) and ethyl acetate extract pretreated group(CTE). The ratio of liver weight per body weight and the activity of GPT in hexane extract group(CTH) were lowest, similar to the results of S. Godulbaegi n-hexane extract(IS) groups intoxicated by $CCl_4$ had lower values of MDA than CS and CT which are control groups. Histological finding of liver tissue revealed less of necrosis in IS extracts groups than in control groups(CS, CT). From these results, IS extracts could predominently prevent hepat-otoxicity of rats. Especially, hexane extract was effective on the detoxication of liver injury among the other extracts.

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Study on the Protective Effect of Corni Fructus Against Free Radical Mediated Liver Damage (산수유의 유리자유기에 의한 간손상 보호효과 및 기전에 대한 연구)

  • Ha, Ki-Tae;Kim, Young-Mi;Kim, Cheorl-Ho;Choi, Dall-Yeong;Kim, June-Ki
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.1
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    • pp.82-88
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    • 2008
  • We evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), in an experimental model of hepatotoxicity induced by carbontetrachloride $(CCl_4)$. The CF exhibited a hepatoprotective activity against Chang cell. And The expression of cytochrome P450 2E1 (CYP2E1), measured by RT-PCR and western blot, was significantly decreased in the CF treated Chang cell. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and downregulation of CYP2E1 expression.

Differential Diagnosis of Chemical-induced Hepatobiliary Toxicities Using a New Hepatobiliary Imaging Agent in Mice

  • Ryu, Chong-Kun;Pie, Jae-Eun;Choe, Jae-Gol;Cheon, Joon;Sohn, Jeong-Won;Jurgen Seidel;David S. Paik;Michael V. Green;Chang H. Paik;Kim, Meyoung-Kon
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.1-8
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    • 2001
  • We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

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