• Title/Summary/Keyword: CCl$^4$

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The Protective Effects of Curcuma longa Linn. Extract on Carbon Tetrachloride-Induced Hepatotoxicity in Rats via Upregulation of Nrf2

  • Lee, Hyeong-Seon;Li, Li;Kim, Hyun-Kyung;Bilehal, Dinesh;Li, Wei;Lee, Dong-Seok;Kim, Yong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.20 no.9
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    • pp.1331-1338
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    • 2010
  • This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene(BHT) for 14 days before $CCl_4$ administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of $CCl_4$ (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the $CCl_4$-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the $CCl_4$-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the $CCl_4$-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against $CCl_4$-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.

Therapeutic Effect of Hovenia dulcis Thunberg Extracts and 6 Types Herbal Extracts on $CCl_4-induced$ Chronic Organ Damages in the Rats-Liver and Kidney (Carbon Tetrachlorid으로 유발된 Rat의 만성 장기(간, 신장) 손상시 헛개나무열매 추출물등 6종 생약의 투여시 조직병리학적변화)

  • Lim, Mee-Kyoung;Kim, Joo-Wan;Kim, Hong-Tae;Lee, Byoung-Je;Ku, Sae-Kwang;Kang, Mi-Young;Lee, Keun-Woo
    • Journal of Veterinary Clinics
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    • v.24 no.3
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    • pp.384-391
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    • 2007
  • This study was conducted to clarify the effects of the Korean raisin (Hovenia dulcis Thunb) extracts and polyherbal extracts consisted of 6 types herbal extracts including HDT (HDTmix) on $CCl_4$ induced organ damages. Extracts were prepared by autoclave ($121^{\circ}C$, 15 psi, 3 hours) and filtered with nylon cloth and filter paper then freezing dried. Male Sprague-Dawley rats $(200^{\circ}{\ae}20g)$ were used as experimental groups, which were divided into 5 groups; intact control group (100 mg/kg), $CCl_4$ dosing group (100 mg/kg), $CCl_4$ dosing after HDT extract dosing group (100 mg/kg), $CCl_4$ dosing after HDTmix dosing group (100 mg/kg), Silymarin dosing group (5 mg/kg) after all test articles were orally dosed once a day for 28 days. They were sacrifiled under ether anesthesia. HDT extracts and HDTmix dramatically inhibits the $CCl_4$ intoxicated hepato/nephropathies with immuno-suppress changes on the spleen. They showed more dramatical protective effects on most of specific organs compared to that of Silymarin 5 mg/kg except for hepatoprotective effects in which, quite similar effects were detected. In addition, HDT extracts showed synergic effects with other types of herbal extracts because HDTmix showed more favorable protective effects on the all specific organs showing $CCl_4-related$ histopathological changes compared to HDT extracts.

The Acute Toxicity of Liocolae vermiculus Extract in Mice and its Effect on Hepatic Damages induced by $CCl_4$ in Rats (제조 엑기스의 마우스 급성독성(急性毒性) 및 흰쥐의 사염화탄소(四鹽化炭素) 간장장애(肝臟障碍)에 미치는 영향(影響))

  • Chung, Myung-Hyun;Kang, Soo-Chul;Kim, Gyung-Wan
    • Korean Journal of Pharmacognosy
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    • v.22 no.1
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    • pp.36-44
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    • 1991
  • This study was attempted to investigate the acute toxicity of Liocolae vermiculus(Liocola brevitarsis) extract in mice, the effect on GOT, GPT Al.p, LDH activities and level of total cholesterol in serum of $CCl_4-intoxicated$ rats. In acute toxicity test, Liocolae vermiculus extract showed 10% mortality at 2,000 mg/kg, p.o. and at 1,000 mg/kg, i.p.. The Liocolae verculus extract caused a remarkable decrease in serum transaminase as well as Al.p activities in $CCl_4-intoxicated$ rats at $300{\sim}1,000{\;}mg/kg$ dosage ranges. The activities of -LDH and the level of total cholesterol were significantly decreased in all sample-treated group, when compared with the control group. The body weight decreased, and the liver and spleen weight increased in $CCl_4-intoxicated$ rats were significantly recovered by the administration of the extracts.

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The Cytotoxicity of Rat Hepatocytes on Viscum album Lectin (겨우살이 lectin의 흰쥐 간세포 독성에 미치는 영향)

  • Chang, Choul-Soo;Ryu, Jae-Ki;Kim, Tae-Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.39 no.3
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    • pp.190-195
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    • 2007
  • In the present study, the author investigated to the cytotoxocity in cultured rat hepatocytes of Viscum album lectin. The cytotoxcity effect in Viscum album lectin on the activity of LDH was also investigated. Viscum album lectin significantly increased LDH leakage into medium of hepatocytes treated or untreated with $CCl_4$ (p<0.001). However, Viscum album lectin significantly increased LDH leakage from $CCl_4$-induced hepatocyte (p<0.001). There was a significant increase in LDH levels relative to the control group. Histological observation basically supported the result obtained from LDH assay. The livers of rats challenged with $CCl_4$ produced a marked increased cytoplasmic vacuoles and inflammatory cells in number, while the number of necrotic cells and swollen hepatocytes did not change significnatly. Rats administered DMSO alone did not alter the normal hepatic architecture. Histological observation of liver section in rat treated 72 hrs with either Viscum album lectin $CCl_4$-induced liver damage showed number of cytoplasmic vaculoe and necrotic cell. The number of inflammatory cell increased markedly. This results suggest to the conclusion that Viscum album lectin has a effect of hepatotoxicity activator.

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Effect of Carbon Tetrachloride Administration on the Serum and Liver Xanthine Oxidase Activity in Ethanol-Pretreated Rats (Ethanol을 전처리한 흰쥐의 간 및 혈청 Xanthine Oxidase 활성에 미치는 사염화탄소의 영향)

  • 윤종국;김병렬;이상일
    • Journal of Environmental Health Sciences
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    • v.19 no.2
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    • pp.69-77
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    • 1993
  • In the present study, the comparison of liver damage in carbon tetrachloride (CCl$_4$)-treated rats with that those pretreated with ethanol and an effect of liver injury on the serum and liver xanthine oxidase (XOD) activity were evaluated. The increasing rate of liver weight per body wt., the levels of serum alanine aminotransferase, and the decreasing rate of hepatic glucose-6-phosphatase activity and the protein contents in the liver cell were higher in carbon tetrachloride-treated animals pretreated with ethanol than the carbon tetrachloride-treated group. Especially, the histopathological findings also showed more severe liver damage in the ethanol-pretreated rats than the rats treated with carbon tetrachloride only. In such a experimental condition the xanthine oxidase activity of serum and liver both of carbon tetrachloride-treated rats and those pretreated with ethanol were higher than that of each control group. And the increasing rate of xanthine oxidase enzyme activity to the control group was higher in carbon tetrachloride-treated group pretreated with ethanol than those treated with CCl$_4$. In addition, the heptic uricase activity and the serum levels of uric acid were more increased in carbon tetrachloride-treated group pretreated with ethanol than those in the CCl$_4$-treated rats. On the other hand, there were no statistical differences in hepatic catalase and glutathione S-transferase activities between the CCl$_4$-treated rats and those pretreated with ethanol. In conclusion, it is assumed that the more severe liver damage in ethanol pretreated rats would be due to oxygen free radical produced by the xanthine oxidase system.

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Hepatoprotective and free radical scavenging activities of Lagerstroemia speciosa Linn. leaf extract

  • Thambi, Priya;Sabu, Mandumpal Chacko;Chungath, Jolly
    • Advances in Traditional Medicine
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    • v.9 no.3
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    • pp.225-231
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    • 2009
  • The present study deals with the amelioration by Lagerstroemia speciosa Linn. leaf extract against hepatotoxicity induced by carbon tetrachloride ($CCl_4$), which was evaluated in terms of serum marker enzymes like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, serum total bilirubin, total protein levels along with concomitant hepatic and antioxidants like superoxide dismutase, catalase, glutathione, glutathione peroxidase and lipid peroxidation enzymes were monitored. These biochemical parameters altered by the single dose level of $CCl_4$ (0.75 ml/kg body weight, i.p). Pre treatment with L. speciosa prior to the administration of $CCl_4$, at the doses of 50 and 250 mg/kg. body weight/day, p.o. for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels, respectively. Silymarin was used as a reference standard, prior to the administration of $CCl_4$ to rats. These findings indicate the protective potential of L. speciosa against hepato toxicity which possibly involve mechanism related to its ability of selective inhibitors of (reactive oxygen species like antioxidants brought about significant inhibition of TBARS suggesting possible involvement of $O_2{\cdot}-$, $HO_2{\cdot}$, and ${\cdot}OH$. In conclusion, the amelioration may be attributed to the synergistic effects of its constituents rather than to any single factor as the leaves are rich in tannins, sterols, flavonoids, saponins etc.

Protective Effects of Galangin on Carbon tetrachloride-Induced Hepatotoxicity (사염화탄소에 의해 유발된 간독성에 대한 galangin의 보호효과)

  • Jung, Bae-Dong;Kim, Cheon-Ho;Kim, Jung-Han;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.40 no.3
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    • pp.320-325
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    • 1996
  • In order to evaluate the protective effects of galangin on $CCl_4$-induced hepatotoxicity, GOT, GPT and malondialdehyde(MDA) values were measured in ICR mice. Galangin,a flavonoid compound, was administered orally for six days and immediately $CCl_4$ was injected intraperitoneally after the last dose of galangin. Mice were sacrificed at 24h after the administration of $CCl_4$. In the multiple pre-treatments for 6 consecutive days, galangin showed more potent protective effects than silymarin as reference active compound in serum GOT, GPT and MDA values in the liver at all doses tested. Antioxidative activity was determined by measuring the amounts of MDA formed from ethyl linoleate by $H_2O_2$ in vitro. Galangin showed higher inhibition than silymarin. These results demonstrate a possible hepato-protective role of galangin against $CCl_4$-induced hepatotoxicity in vivo and $H_2O_2$-induced lipid peroxidation in vitro. Therefore, galangin may be capable of protecting hepatotoxicity.

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Antioxidant Activities of Isoflavones from the Rhizomes of Belamcanda chinensis on Carbon Tetrachloride-Induced Hepatic Injury in Rats

  • Jung, Sang-Hoon;Lee, Yeon-Sil;Lim, Soon-Sung;Lee, Sanghyun;Shin, Kuk-Hyun;Kim, Yeong-Shik
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.184-188
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    • 2004
  • The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit hepatic damage induced by carbon tetrachloride ($CCl_4$)-intoxication in rats by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by $CCl_4$-intoxication in rats, as well as in a lipid peroxidation causing a significant decrease in malondialdehyde (MDA) production by thiobarbituric acid (TBA)-reactant assay. Both compounds also showed strong increase in the antioxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities in $CCl_4$-intoxicated rats. These results suggested that tectorigenin and tectoridin isolated from the rhizomes of B. chinensis possess not only the antioxidative, but also the hepatoprotective activities in $CCl_4$ -intoxicated rats.

Regulatory Mechanism of Cytochrome P450IIE in the Rat with Hepatic Injury and Ketosis (간장장해와 Ketosis시에 Cytochrome P450IIE의 Regulatory Mechanism에 관한 연구)

  • 윤여표;강원식;이세창;손동환
    • Journal of Environmental Health Sciences
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    • v.19 no.3
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    • pp.58-63
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    • 1993
  • In order to elucidate the alteration of drug-metabolizing enzymes and mechanism in the animal with hepatic injury and ketosis, the regulation of P450IIE was studied in the rats with heaptic injury caused by CCl$_4$ and with ketosis caused by streptozotocin and high-fat diet. P450IIE expression in liver was examined by the combination of enzyme activities, Western immunoblot, and mRNA Northern blot analyses using specific polyclonal antibody and cDNA probe for P450IIE. Enzyme activity and amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl$_4$ . However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl$_4$ were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl$_4$. The enzyme activities (aniline hydroxylase) in hepatic microsomes were elevated about 2-3-fold by streptozotocin and feeding with a high fat diet. This increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. Our data thus indicated that P450IIE induction during the ketosis appears to be due to pretranslational activation.

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Hepatoprotective activity of Indigofera aspalathoides extract against CCl4-induced liver damage

  • Gupta, M.;Mazumder, U.K.;Haldar, P.K.;Manikandan, L.;Senthilkumar, G.P.;Kander, C.C.
    • Advances in Traditional Medicine
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    • v.4 no.2
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    • pp.100-103
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    • 2004
  • The plant Indigofera aspalathoides are used by a large number of tribes in India for the treatment of various hepatic disorder. The methanol extract of Indigofera aspalathoides (MEIA) was evaluated for its effect on carbontetrachloride $(CCl_{4})$ induced liver damage. Biochemical parameters such as serum glutamine oxaloacetate trasaminase (SGOT), serum glutamine pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), total serum protein (TP), thiobarbituric acid reactive substances (TBRS) and glutathione content of the liver were estimated to assess liver function and metabolism. Biochemical observations suggest that methanol extract of Indigofera aspalathoides (MEIA) significantly restored the liver function and metabolism towards normal condition in $CCl_{4}$-induced hepatic damage.