• Title/Summary/Keyword: $CCl_4$-induced hepatotoxicity

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Effect of G009 on $CCl_4-Induced$ Hepatic Injury and Lipid Peroxidation in Rats (G009가 $CCl_4$로 유발된 간손상 및 지질 과산화에 미치는 영향)

  • Jeong, Hoon;Han, Man-Deuk;Baek, Sung-Jin;Kim, Yong-Seok;Kang, Sang-Mo;Lee, June-Woo
    • Korean Journal of Pharmacognosy
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    • v.27 no.3
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    • pp.159-166
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    • 1996
  • To evaluate hepatoprotective effects of G009, an hepatoprotective agent which was extracted from the mycelia of Ganoderma lucidum IY009, we were, studied using $CCl_4$-and galactosamine-induced hepatotoxicity in rats. The ratio of liver weight to body weight, the value of glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase (GPT) activities, the change of a lipids in serum, and the inhibitory activity of malondialdehyde (MDA) formation in serum and liver homogenate were determined in rats. G009 was not significantly changed of the ratio of liver weight to body weight and the content of lipids in serum, but reduced the serum GOT and GPT values in $CCl_4$-and galactosamine-induced hepatotoxicity in rat. Especially, protective effect of G009 on rat hepatic injuries induced by galactosamine was significantly appeared. $CCl_4$ increased markedly the formation of lipid peroxides in the liver homogenate, and serum. The increase of lipid peroxides by $CCl_4$-induced hepatotoxicity was markedly reduced by the treatment with G009. These results suggest that the hepatoprotective effects of G009 may be correlated with its anti-lipid peroxidative activity, therefore, it may be potential agent for hepatic disease.

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Protective Effect of Administrated Glutathione-enriched Saccharomyces cerevisiae FF-8 Against Carbon Tetrachloride ($CCl_4$)-induced Hepatotoxicity and Oxidative Stress in Rats

  • Shon, Mi-Yae;Cha, Jae-Young;Lee, Chi-Hyeoung;Park, Sang-Hyun;Cho, Young-Su
    • Food Science and Biotechnology
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    • v.16 no.6
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    • pp.967-974
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    • 2007
  • The present work is aimed to evaluate the protective effect of glutathione-enriched Saccharomyces cerevisiae FF-8 strain on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and oxidative stress in rats. The activities of liver markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase), lipid peroxidative index (thiobarbituric acid-reactive substances), and the antioxidant status (reduced glutathione) were used to monitor those protective roles of FF-8 strain. The liver marker enzymes in plasma and the lipid peroxidation in the liver were increased when $CCl_4$ was treated but these were significantly decreased by FF-8 strain treatment. The hepatic concentration of glutathione in the current glutathione-enriched FF-8 strain fed animal was approximately twice as high as the normal, but this was slightly increased in response to $CCl_4$ plus glutathione-enriched FF-8 strain. The increased liver triglyceride concentration due to the $CCl_4$ treatment was significantly decreased by FF-8 strain and the reduced level reached to that of normal group. Administration of FF-8 strain in normal rat did not show any signs of harmful effects. Therefore, the current findings suggest that FF-8 strain could be an effective antioxidant with no or negligible side-effects and it might be useful for the purpose of protection treatment of hepatotoxicity and oxidative stress in $CCl_4$-treatment in rat.

Anti-oxidant activities of kiwi fruit extract on carbon tetrachloride-induced liver injury in mice

  • Kang, Wonyoung;Yang, Heekyoung;Hong, Hyun Ju;Han, Chang Hoon;Lee, Young Jae
    • Korean Journal of Veterinary Research
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    • v.52 no.4
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    • pp.275-280
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    • 2012
  • The kiwi (Actinidia deliciosa) is well known to contain anti-oxidants. In this study, we investigated the anti-oxidant effects of kiwi extract on carbon tetrachloride ($CCl_4$) induced liver injury in BALB/c mice. The radical scavenging effect of 80% methanol extract of Halla-Gold kiwi was observed. For the animal study, mice were randomly divided into four groups: normal group, $CCl_4$-induced model group, kiwi extract administered group, and silymarin treated group. The kiwi extract was provided daily for 10 days. At the 24 h after last administration, $CCl_4$ was injected. The kiwi extract showed strong inhibitory effect of DPPH radicals and superoxide scavenging. In animal study, administration of $CCl_4$ resulted in significantly elevated plasma levels of ALT and AST but they decreased in kiwi-extract pretreated group. Anti-oxidant enzymes such as GSH-px and GSH-rd were restored in the kiwi extract treatment group. Histopathological degeneration was also prevented in the kiwi extract treated group compared with of the control group, which exhibited $CCl_4$-induced hepatotoxicity. On the basis of the obtained results, it can be concluded that kiwi extract showed protective effects, not only as anti-oxidant effects, but also in the protection of hepatotoxicity in $CCl_4$-intoxicated mice.

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 $CCl_4$.

Preventive effect of a Schizandrin C derivative DDB-mixed preparation (DWP-04) against hepatotoxicity induced by Carbon Tetrachloride (사염화탄소로 유발된 간독성에 대한 오미자 Schizandrin C 유도체 DDB 복합물 DWP-04의 예방효과)

  • Lee, Jung-Hee;Chi, Sang-Cheol;Kim, Seok-Hwan;Shin, Young-Ho;Park, Hee-Juhn;Choi, Jong-Won
    • Korean Journal of Pharmacognosy
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    • v.36 no.1 s.140
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    • pp.44-49
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    • 2005
  • The protective effects of the DWP-04 [DDB : selenium yeast: glutathione {31.1 : 6.8 : 62.1 (%, w/w)} against hepatotoxicity by carbon tetrachloride $(CCl_4)$ were studied in rats. The rats were intraperitoneally injected with $CCl_4$ (50% in com oil) at initial dose of 1 ml/kg followed by 0.5 ml/kg 3 times during 1 week. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was administered everyday before the start of $CCl_4$ injection for two weeks. $CCl_4$ induced hepatocelluar degeneration and necrosis, which led to a great increase in serum aminotransferase, alkaline phosphatase activity and serum lipid levels. It was found by biochemical analysis that $CCl_4$ treatment remarkably increased thiobarbituric acid reactive substances and physphatidylcholine hydroperoxide in hepatic tissues and induced antioxidant enzymes such as catalase and superoxide dismutase (SOD). Liver and serum lipids were significantly lower in rats fed on DWP-04 than in rats induced by $CCl_4$ only-treatment. These results suggested that the DWP-04 could be a promising candidate for the protection of liver injury based on the preventive effects against lipid peroxidation and serum biochemical parameters.

Hepaprotective Effect of Standardized Ecklonia stolonifera Formulation on CCl4-Induced Liver Injury in Sprague-Dawley Rats

  • Byun, Jae-Hyuk;Kim, Jun;Choung, Se-Young
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.218-223
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    • 2018
  • The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

Effect of Onion Extract on the Carbon Tetrachloride-induced Liver Injury in Mouse

  • Lee, Kyung-Jin;Kim, Deok-Song;Kim, Jong-Sun;Chin, Jong-Eun;Kim, Jun-Ho;Na, Myung-Suk;Lee, Jong-Bin
    • Preventive Nutrition and Food Science
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    • v.8 no.2
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    • pp.130-136
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    • 2003
  • The protective effects of onion extract (OE), onion powder extracted in ethanol for 2 days. on carbon tetrachloride ($CCl_4$)-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with OE prior to the administration of $CCl_4$ significantly reduced the increase in serum alanine and aspartate aminotransferase activities and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with OE significantly prevented the depletion of reduced glutathione content in the liver of $CCl_4$-intoxicated mice. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic findings. The effects of OE on the cytochrome P450 (P450) 2E1, the major isozyme involved in $CCl_4$ biotransformation were investigated. Treatment of mice with OE resulted in a significant decrease in P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. OE also exhibited antioxidant effects in FeCl$_2$-ascorbate induced lipid peroxidation in rat liver homogenates and in superoxide radical scavenging activity. These results show that the protective effects of OE against the $CCl_4$-induced hepatotoxicity may be due to its ability to block bioactivation of $CCl_4$, mainly tty inhibiting the expression and activities of P450 2E1 and by scavenging free radicals.

Protective Effects of Angelica tenuissima Nakai on Hepatotoxicity by Carbon Tetrachloride in Rats (사염화탄소에 의한 간손상에 미치는 고본의 보호작용)

  • 정춘식;정기화
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.211-217
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    • 2002
  • Hepatoprotective activity of methanol extract of Angelica tenuissima Nakai on the $CCl_4$-induced hepatotoxicity was investigated. To elucidate the hepatoprotective activity and free radical scavenging effect, we examined alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total protein, cholesterol, malondialdehyde (MDA) levels in serum and activities of superoxide dismutase (SOD), catalase (CAT) in hepatic tissue as compared with those of carbon tetrachloride-induced rats. The action mechanism also has been estimated by quantative analysis of cytochrome P450 (CYP), NADPH-CYP reductase for phase I metabolism and glutathion (GSH), glutathion S-transferase (GST) level for phase II metabolsim. Treatment of Angelica tenuissima methanol extract significantly lowered the levels of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol, triglyceride, MDA, CAT were decreased, and SOD was activated. This result indicates that the hepatoprotective effect of Angelica tenuissima methanol extract on the CCl4-induced hepatotoxicity would be originated from reduction of the NADPH-CYP reductase, GSH and the enhancement of the activities of GST, CYP.

Influence of Thyroxine on the Hepatotoxicity of Carbon Tetrachloride ($CC1_4$의 간장독작용(肝臟毒作用)에 미치는 Thyroxine의 영향(影響))

  • Hong, Ki-Sung;Cheon, Yun-Sook
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.31-38
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    • 1980
  • Calvert et al. formulated the hypothesis that carbon tetrachloride ($CCl_4$) acted on the central nervous system to produce and intensify sympathetic discharge which resulted in anoxic necrosis of the liver. Recknagel suggested that the essential feature of $CCl_4$ hepatotoxicity depended on the cleavage of it to $CCl_3$(free radical) and the peroxidative decomposition of cytoplasmic membrane structural lipids. And there are many reports which show the increase of adrenergic activity in hyperthyroidism. In this paper, the influence of thyroxine on the hepatotexicity of carbon tetrachloride was investigated in mice. The results obtained were summarized as follows; 1) Hepatic total lipid and lipid peroxide contents were slightly decreased by L-sodium thyroxine injection(4mg/kg/day for 4days or 6days), but hepatic glycogen content was significantly decreased. 2) Hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were significantly increased by $CCl_4$ (4 ml/kg single dose or triple dose: 4ml/kg/day for 3days), but hepatic glycogen content was significantly decreased. 3) The increase of hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity induced by $CCl_4$ were significantly inhitited by the pretreatment of thyroxine. 4) The decrease of hepatic glycogen induced by $CCl_4$ was not affected by the pretreatment of thyroxine.

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인삼, 한국 및 중국산 산양삼의 간 보호 효능에 관한 실험적 연구

  • Kim, Young-Jin;Park, Hee-Soo;Kwon, Ki-Rok;Kim, Ho-Hyun
    • Journal of Pharmacopuncture
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    • v.10 no.1 s.22
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    • pp.101-107
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    • 2007
  • Objectives : This study was aimed at investigating liver protection mechanism of Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese by inducing liver toxicity through $CCl_4$ and t-BHP in mice and evaluated serological findings. Methods : Experiment groups was categorized into untreated normal group, treated control group, and orally administered Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese experimental groups. At the termination of experiment, gross examination of the liver as well as Total bilirubin, AST, and ALT contents in the serum were evaluated. Results : 1. In the $CCl_4$ induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. 2. In the t-BHP induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. Conclusion : Taken together, Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese cannot be effectively used for recovering the liver functions in acute hepatotoxicity tests using $CCl_4$ and t-BHP. Further researches, for example treated long period, must be tried to verify the efficacies.