• Title/Summary/Keyword: rat hepatotoxicity

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The Effect of Lithospermi Radix on Benzo(a)pyrene-Induced Hepatotoxicity (Benzo(a)pyrene에 의해 유도된 간기능장해에 미치는 자근 추출액의 영향)

  • 윤수홍;박은주;오관현;정영건;권오진
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.2
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    • pp.144-148
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    • 1993
  • The present study was undertaken to compare the pharmacological activities of crude Lithospermi radix reported with the clinical uses in the oriental medicine. Crude Lithospermi radix uesd for the treatment of burn, eczema, blister, diuretic, scarlet fever and septicemia as antipyretic, antidotic and antiphlogistics. Therefore we tested the effects of Lithospermi radix water extract on the liver-protective activities in the rats. The results obtained from enzyme assay, measurement of serum and liver alanine. aspartate aminotransferase(ALT, AST) and lipid composition indicated that Lithospermi radix water extract showed significant liver-protective activities against benzo(a)pyrene-induced hepatotoxicity.

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Protective Effect of Eriobotrya japonica Lindl. on Hepatotoxicity by Carbon Tetrachloride (비파식초의 사염화탄소에 의한 간독성 보호 효과)

  • Shin, Yu-Bin;Ha, Bae-Jin
    • Journal of Food Hygiene and Safety
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    • v.33 no.1
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    • pp.77-82
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    • 2018
  • This study was carried out to investigate the effect of natural Eriobotrya japonica Lindl. vinegar on the liver protective effect of animals exposed to carbon tetrachloride. Eriobotrya japonica Lindl. vinegar (200 mg/kg) was administered at the same time for 28 days, and hepatotoxicity was induced by intraperitoneal injection of carbon tetrachloride on the $29^{th}$ day. The aspartate aminotransferase and alanine aminotransferase levels were significantly decreased (p < 0.001) and the superoxide dismutase and catalase activities were significantly increased (p < 0.001) in the Eriobotrya japonica Lindl. vinegar group compared to the control group. Histopathological observations showed that the Eriobotrya japonica Lindl. vinegar showed hepatic cell structure similar to normal group, and these results showed that it had an effect of suppressing and protecting the damage of liver cell. Therefore, Eriobotrya japonical Lindl. vinegar is considered to be a healthy functional food of the liver.

Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats

  • Zolfagharzadeh, Fatemeh;Roshan, Valiollah Dabidi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2931-2936
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    • 2013
  • Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 $mg.kg^{-1}$) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

Effect of Daewhang-whangryunhaedok-Tang on Carbon Tetrachloride-induced Hepatotoxicity and Acute Toxicity (대황황련해독탕의 사염화탄소 유발 간장해 보호효과 및 급성독성)

  • Kim, Young-Suk;Jung, Eun-Ah;Chang, Jong-Chul;Yang, Hyung-Kil;Cho, Gi-Ho;Bae, Hyung-Sup;Lee, Kyung-Sup;Kim, Dong-Hyun;Kim, Nam-Jae
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.5-12
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    • 2002
  • This study was performed to evaluate hepatoprotective effect of Daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by $CCl_4$ and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase (LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid peroxidation, catalase and glutathione-S-transferase(GST) in liver microsome were determined in hepatotoxic rats induced by $CCl_4$ DWT DWT was significantly reduced the serum ALT, AST, ALP, LDH, TC and TG levels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of $CCl_4$-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5,000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks. DWT did not induce any toxic signs in the mortalities, clinical signs, body weight changes, and gross necropsy findings of mice. Based on these results, it is concluded that DWT may have the hepatoprotective effect on $CCl_4$ induced hepatotoxicity in rats. Also, DWT may have no side effect and its $LD_{50}$ value may be over 5,000 mg/kg b.w. in mice.

The protective effect of the MeoH extract of Ikhwangsan against galactosamine-induced hepatotoxicity in rat (익황산(益黃散)이 galactosamine으로 유도(誘導)한 간중독((肝中毒) 흰쥐에 미치는 영향(影響))

  • Kim, Mi-Ji;Kim, Jang-Hyun
    • The Journal of Dong Guk Oriental Medicine
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    • v.5
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    • pp.167-186
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    • 1996
  • This study aimed to evaluate the protective effect of the MeoH extract of Ikhwangsan against galactosamine-induced hepatotoxicity. In the experiments, after treated with Ikhwangsan methanol extract to the rats for 15days and then induced hepatotoxicity with galactosamine for 2days. Then content of glutathione, level of lipid peroxide and activity of GOT GPT in the hepatic tissue, activity of GOT GPT ${\gamma}$-GTP ALP and ratio albumin/globulin in serum were measured. The results were obtained as followed : 1. The content of hepatic glutathione was significantly reduced by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably increased. 2. The level of hepatic lipid peroxide was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 3. The activity of GOT GPT in the hepatic tissue was significantly constrained by galactisamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably increased. 4. The activity of GOT GPT in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 5. The activity of ${\gamma}$-GTP in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was reduced. 6. The activity of ALP in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 7. The ratio albumin/globulin in serum was reduced by galactosamine. The test group which have been pre-treated by Ikhwangsan was increased.

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Optimal Level for the Protection of Carbon Tetrachloride-induced Sprague-Dawley Rat Liver Damage by Mycelial Cultures of Lentinus edodes (Sprague-Dawley 쥐의 사염화탄소 유도 간 손상에 대한 표고버섯균사체의 효과)

  • Jang, Wook-J.;Kim, Young-S.;Ha, Yeong-L.;Park, Cherl-W.;Ha, Young-K.;Kim, Jeong-O.
    • Journal of Life Science
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    • v.20 no.5
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    • pp.782-788
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    • 2010
  • The protective effects of a powder mixed with solid-cultured and liquid-cultured Lentinus edodes mycelia (2 : 1, w/w) (designate LED) with different doses of carbon tetrachloride ($CCl_4$) on induced hepatotoxicity in male Sprague-Dawley (SD) rats was investigated. The rats were divided into seven groups (6 rats/group) and the following substances were administered orally to each group: Vehicle (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 100, 200, 300 and 400 mg/kg BW in 0.2 ml distilled water), and Silymarin (200 mg/Kg BW in 0.2 ml distilled water). After two weeks of daily administration, all groups except for the Vehiclegroup were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1 : 1 v/v; 0.5 ml/kg BW). One day later, blood and liver samples were collected to analyze biomarkers. All LED treatments elevated hepatic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH peroxidase) activities, and reduced thiobarbituric reactive substances (TBARS), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6), resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic acid dehydrogenase (LDH) activities in plasma. These results indicate that LED effectively protected SD rat hepatotoxicity induced by $CCl_4$ through its antioxidative activity and reduction of some cytokines. The highest efficacy was found in LED 200 mg/kg BW, showing potential as a useful material for protection from hepatotoxicity in humans.

Gene Expression Analysis of Methotrexate-induced Hepatotoxicity between in vitro and in vivo

  • Jung, Jin-Wook;Kim, Seung-Jun;Kim, Jun-Sup;Park, Joon-Suk;Yeom, Hye-Jung;Kim, Ji-Hoon;Her, Young-Sun;Lee, Yong-Soon;Kang, Jong-Soo;Lee, Gyoung-Jae;Kim, Yang-Seok;Kang, Kyung-Sun;Hwang, Seung-Yong
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.256-261
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    • 2005
  • The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

Effects of Rhei Rhizoma, Ephedrae Herba and Scutellariae Radix on the Metabolism of 7-Ethoxycoumarin in Isolated Rat Liver (적출관류 간에서 대황, 마황 및 황금이 7-에톡시쿠마린의 대사에 미치는 영향)

  • Choi, Ki-Hwan;Kim, Soon-Sun;Park, Youn-Joo;Chung, Hye-Joo;Ahn, Mee-Ryung;Seo, Soo-Kyung;Sheen, Yhun-Yhong;Kim, Dong-Sup;Chang, Young-Sup
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.422-430
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    • 1998
  • In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-e thoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however, 7-hydroxycoumarin was increased in Ephedrae herba pretreated rats (p<0.01). We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 and P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYP1A1 and CYP2B1 mRNA level was increased, which was was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma, Ephedrae herba and Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pretreated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05), while histopathological examination performed after liver perfusion did not show any difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated by CYP1A1 mRNA induction.

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Experimental Study on the Cannabis Fructus on Exercise Capacity and Cognitive Function in Vascular Dementia Rat Model (마자인(麻子仁)이 치매병태모델의 운동과 인지기능에 미치는 실험적 연구)

  • Bae, Kil-Joon;Song, Min-Yeong;Choi, Jin-Bong;Kim, Seon-Jong
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.1
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    • pp.1-15
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    • 2015
  • Objectives The aim of this study was to investigate the effects of Cannabis Fructus on exercise capacity and cognitive function in chronic hypoperfusion induced vascular dementia rat model. Methods Vascular dementia rat models were induced by chronic cerebral hypoperfusion through bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal group; control group; CF I group (feeding Cannabis Fructus 100 mg/kg); CF II group (feeding Cannabis Fructus 300 mg/kg). In order to study the effects of oral administration of Cannabis Fructus on vascular dementia rat models, corner turn test, hole board test, radial arm maze test, passive avoidance test were taken and Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, serum of Vascular endothelial growth factor (VEGF) protein level were measured. Also histological findings of the liver, kidney, brain and the change of Tau immunoreactive neurons in hippocampus were observed. Results CF I and CF II showed significant improvement in corner turn test, hole board test, radial arm maze test, passive avoidance test, Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, the serum of Vascular endothelial growth factor (VEGF) protein level and the change of Tau immunoreactive neurons in hippocampus. CF I showed more significant effect than CF II in these tests. However in histological observations of the liver and kidney both CF I and CF II showed glomerular injury and hepatotoxicity. Conclusions These results suggest that Cannabis Fructus was helpful in improving exercise capacity and cognitive function on Chronic hypoperfusion induced Vascular Dementia rats. However Cannabis Fructus affects the liver and kidney, therefore suggest that this is an area for further study.

Effect of Green Tea Catechin on Acute Hepatotoxicity in Rats (랫트의 간 손상에 대한 녹차카테킨의 보호 및 치료효과)

  • Yuk, Dong-Yeon;Lee, Mi-Yea;Yun, Yeo-Pyo
    • Journal of Food Hygiene and Safety
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    • v.19 no.3
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    • pp.105-111
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    • 2004
  • Green tea catechin (GTC) is known to have a wide variety of pharmacological activites. In the present study, the effects of GTC on acute hepatotoxicity induced by carbon tetrachloride ($CCl_4$) and galactosamine were examined in rats. Two doses (50 or 100 mg/kg) of GTC were administered to rats orally for 3 days befor or after the induction of hepatotoxicity. A hepatotoxicity was induced by the inpraperitoneal injection of the $CCl_4$ (0.5 ml/kg) or galactosamine (400 mg/kg). GTC(50 mg/kg) reduced the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level of the $CCl_4$-intoxicated rats in the pre-treatment group (from 262${\pm}$11, 80${\pm}$19 to 153${\pm}$22, 55${\pm}$25), and also in the post-treatment group (from 156${\pm}$40, 105${\pm}$3 to 106${\pm}$22, 55${\pm}$9), respectively. And GTC (50 mg/kg) also reduced the levels of AST and ALT in both pre-treatment (from 576${\pm}$24, 276${\pm}$68 to 236${\pm}$13, 115${\pm}$13) and post-treatment (from 233${\pm}$54, 137${\pm}$11 to 119${\pm}$23, 44${\pm}$17) when induced by galactosamine. GTC also showed the inhibition of pathogenesis of hepatocyte of $CCl_{4^-}$ and galatosamine-intoxicated rat. These results suggest that green tea catechin (GTC) may be useful fur the prevention and therapy of hepatotoxic pathogenesis.