• Title/Summary/Keyword: Hepatotoxicity

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Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice

  • Kim, Dong-Wook;Cho, Hong-Ik;Kim, Kang-Min;Kim, So-Jin;Choi, Jae-Sue;Kim, Yeong-Shik;Lee, Sun-Mee
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.406-412
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    • 2012
  • This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride ($CCl_4$)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after $CCl_4$ injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin-3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. $CCl_4$ increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

Methanol Extract of Agaricus blazei Murill Reduces Hepatic Damage Induced by $CCl_4$ and High Fat and Improves Liver Lipid Profile in Rats

  • Jung, Myung-Eun;Kwon, Hyuck-Se;Shin, Se-Gye;Jin, Yong-Xie;Han, Eun-Kyung;Ham, Seung-Shi;Kang, Il-Jun;Chung, Cha-Kwon
    • Nutritional Sciences
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    • v.9 no.4
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    • pp.267-272
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    • 2006
  • The effect of methanol extract from Agaricus blazei Murill on the hepatotoxicity was investigated $CCl_4$ is one of the oldest and most widely used toxins for the induction of hepatic damages and fibrosis in experimental animals. In this study, male Sprague-Dawley(SD) rats were randomly divided into 6 groups of the control(C), $CCl_4(T),\;CCl_4$ and high fat group(TL) with matching sub-groups of Agaricus blazei Murill extract-fed groups of CA, TA and TLA. Methanol extracts of Agaricus blazei Murill were fed 50 mg/kg B.W daily via drinking water. A 1.2 mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total of six times. The levels of total-cholesterol, TG, LDL and LDL-phospholipids were elevated by $CCl_4$ treatment as compared to the control(C). However, Agaricus blazei Murill methanol extract feeding in the group of TA and TLA significantly(p<0.05) decreased TG by 53.1 % and 17.9% compared to the internal control of T and TL, respectively. Triglyceride of TL was increased by 3.33 times(p<0.05) compared to the control(C) with $CCl_4$ and high fat administration from 3.78 mg/g to 12.60 mg/g liver. The extract(CA) also reduced kidney weight compared to the control(C). With the administration of high fat and $CCl_4$(TLA), the extract reduced the organ weight of both liver and kidney and further, significantly reduced TG, total cholesterol and GTP activity. Hepatoprotective effects of Agaricus blazei Murill on GOT, GPT, AP and LDH activities were enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract reconstituted the damaged cytoplasm and stimulated mitochondriogenesis. The above results suggest that Agaricus blazei Murill may have a possible protective effect against chemically induced liver damage and further help to reduce the symptoms of fatty liver.

Effect of Dietary Protein and Fiber on Ethanol-induced Hepatotoxicity in Rats (흰쥐의 에탄올성 간장해에 미치는 식이 단백질과 섬유소의 영향)

  • 조수열;박은미;이미경;장주연;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.4
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    • pp.675-681
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    • 1997
  • This study was conducted to investigate the effect of dietary protein and fiber levels on the activities of ethanol metabolizing enzymes of liver in ethanol-treated rats. Sprague-Dawley male rats were fed on diets containing two levels of protein(7, 20%/kg diet) and pectin(5, 10%/kg diet). In ethanol experiments, ethanol(25% v/v) was administered by oral intubation(5g/kg body weight) at the same time once a day Control animals received an isocaloric dose of sucrose. The rats were sacrificed after 5 weeks of feeding periods. Alcohol dehydrogenase and microsomal ethanol oxidizing system activities of hepatic tissue were increased more in ethanol-treated groups than in control groups. Increment of activities predominated in normal protein normal fiber group. Aldehyde dehydrogenase activity was decreased in ethanol-treated groups and significantly decreased in normal Protein normal fiber group. Cytochrome P-450 content was significantly increased in ethanol-treated groups and Predominated in normal protein groups. Xanthine oxidase activity was increased in ethanol-treated groups, but not significantly except normal protein normal fiber group. Glutathione content tended to increase in proportion to level of dietary protein and was higher in normal fiber groups than in high fiber groups, whereas it was decreased by ethanol treatment. Lipid Peroxide content was significantly increased in low Protein normal fiber groups.

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Eliminatory Effect of Mixture including Hot Water Extract of Dendropanax morbifera Lev. on Alcohol-induced Blood Alcohol Concentration and Hangover in Rat (흰쥐에서 황칠나무 열수 추출물을 포함한 혼합물의 혈중 알코올 농도와 숙취 해소 효과)

  • Na, Ju-ryun;Kim, Eun;Park, Soyi;Lee, Kihoon;Jeong, Eui-seon;Kim, Jinseok;Kim, Youngjae;Kim, Sunoh
    • Journal of Chitin and Chitosan
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    • v.23 no.4
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    • pp.267-276
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    • 2018
  • This study was performed to investigate the ameliorating effect of a hangover beverage mixture (SBJ) that contains Dendropanax morbifera Lev. and several medicinal plant extracts, on hepatoprotection and alcohol-metabolizing enzymes in alcohol-induced hangover in both in vitro and in vivo models. In human hepatoma cell line, HepG2, 300 mM of ethanol-induced hepatotoxicity was significantly improved by pretreatment of SBJ by dose-dependent manner. In the in vivo study, administration of alcohol to rats raised to the concentration of blood alcohol and lactate dehydrogenase (LDH). Blood alcohol and LDH levels in SBJ-treated rats significantly decreased at 0.5 h and 8 h after acute ethanol administration (40%, 4.6 g/kg body weight) as compared to alcohol-treated rats. Hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity were significantly higher in SBJ-treated rats than in alcohol-treated rats. SBJ supplementation reduced formation of malondialdehyde (MDA), and inhibited reductions of hepatic superoxide dismutase (SOD), hepatic glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) levels, compared with rats administered alcohol. Plasma catalase (CAT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels showed unaltered resulted in all experimental groups compared with the control group. These results suggest that SBJ exhibit hepatoprotective properties by enhancing ADH, ALDH activity and stimulating the antioxidant defense system in alcohol-induced hangover.

Protective Effects of Extracts of Protaetia brevitarsis on Carbon tetrachloride-induced Hepatotoxicity in the Mice (사염화탄소에 의해 유발된 흰쥐의 간독성에 미치는 흰점박이꽃무지 추출물의 간보호 효과)

  • Chon, Jeong-Woo;Kweon, HaeYong;Jo, You-Young;Yeo, Joo Hong;Lee, Heui Sam
    • Journal of Sericultural and Entomological Science
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    • v.50 no.2
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    • pp.93-100
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    • 2012
  • To investigate the effects of Protaetia. brevitarsis extracts on the protection against liver damage by carbon tetrachloride($CCl_4$) in rat, two kinds of experiment were performed, firstly by the primary hepatocyte culture and secondly by the animal feeding. The primary hepatocyte culture with the extracts of P.brevitarsis showed significantly low activities of GPT, bile acid, and bilirubin, indicating an excellent protective effect against liver damage by $CCl_4$. Especially, below molecular weight 1,000 blew the water to have 32.1% recovery degree. In the seconde experiment, serum GPT activity was significantly decreased in water fraction of P. brevitarsis compared to $CCl_4$ treatment by 98.2%. Serum concentration of bile acid and bilirubin were tended to increased by $CCl_4$ treatment, but water fraction of P. brevitarsis and silymarin recovered the level. These consistent results in vitro and in vivo suggest that the extracts of P. brevitarsis may have strong protective effects against liver damage induced by the potential toxicants such as $CCl_4$.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

  • Wan, Yan;Wang, Jing;Xu, Jin-feng;Tang, Fei;Chen, Lu;Tan, Yu-zhu;Rao, Chao-long;Ao, Hui;Peng, Cheng
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.617-630
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    • 2021
  • Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Laboratory analysis of acute acetaminophen overdose patients in Emergency Medical Centers: including analysis of one toxicological laboratory data (응급의료센터에서 아세트아미노펜 과다복용 환자의 검사실 분석 현황: 일개 중독분석실 농도 분석자료 포함)

  • Kim, In Chan;Won, Sinae;Lee, Arum;Jung, Haeun;Lee, Jeongsun;Oh, Bum Jin
    • Journal of The Korean Society of Clinical Toxicology
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    • v.19 no.1
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    • pp.31-37
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    • 2021
  • Purpose: Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient's blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs. Methods: We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory. Results: We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years). Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p<0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p<0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p<0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours). The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p<0.01, regional 5.7±0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours). Conclusion: Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.

Massa Medicata Fermentata improves fatty liver in high fat diet-fed nonalcoholic fatty liver disease's mouse model (고지방식이 유도 비알콜성지방간 마우스 모델에서 육신국(六神麯)의 지방간(脂肪肝) 개선효과)

  • Roh, Jong Seong;Lee, Hye Rim;Ahn, Ye Ji;Yoon, Mi Chung;Shin, Soon Shik
    • The Korea Journal of Herbology
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    • v.29 no.2
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    • pp.23-31
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    • 2014
  • Objectives : This study was undertaken to verify the effects of Massa Medicata Fermentata (MMF) on nonalcoholic fatty liver disease (NAFLD) using high fat diet-fed male mice. Methods : Fifty four male C57BL/6N mice (age matched) were used for all experiments. Nine standard chow diet-fed mice were used as normal group and forty five high fat diet-fed obese mice were randomly divided into 5 groups: control, atorvastatin-10mg/kg, MMF(1)-62.5mg/kg, MMF(2)-125mg/kg and MMF(3)-250mg/kg. After all groups were treated with several kinds of diets for 8 weeks, we measured body weight gain, adipose tissue weights, plasma lipid and glucose metabolism, visceral organ weights, histological analysis for liver on the mice. Results : MMF-treated mice had lower body weight gain compared with controls. Among MMF-treated mice, the effect was magnified in MMF(2). MMF(3)-treated mice had lower blood plasma total cholesterol (TC) and glucose level compared with controls. MMF decreased hepatic lipid accumulation, liver fibrosis and liver inflammation of mice compared with controls. The effects was maximized in MMF(2) and atorvastatin. Blood plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyltransferase (${\gamma}$-GT) concentrations tends to be decreased by MMF compared with controls. Blood plasma AST, ALT, ${\gamma}$-GT concentrations and organ weights were not changed by MMF, indicating that all three kinds of MMF do not show any hepatotoxicity. Conclusions : These results suggest that MMF improves NAFLD by reducing body weight gain, hepatic lipid accumulation, liver fibrosis, liver inflammation.

Non-alcoholic fatty liver protective effects, and studies on the mechanism of action of Crataegi Fructus (산사의 NAFLD 보호 효과 및 그 작용기전에 관한 연구)

  • Kim, Min-Chul;Kong, Ryong;Han, Hyoung-Sun;Kang, Dam-hee;Lee, Seung-Jin;Lee, Cheon-Cheon;Wang, Seo;Kwon, Dong-Yeul;Kang, Ok-Hwa
    • The Korea Journal of Herbology
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    • v.33 no.6
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    • pp.61-70
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    • 2018
  • Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

The Efficacy Evaluation of Tourmaline-Ionized Water in Animal Study (투어마린이온활성수의 효능 평가)

  • Yoon, Yang-Suk;Kim, Dong-Heui;Qi, Xu-Feng;Song, Soon-Bong;Jung, Jong-Ho;Joo, Kyung-Bok;Teng, Yung-Chien;Lee, Kyu-Jae
    • Applied Microscopy
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    • v.39 no.4
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    • pp.311-317
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    • 2009
  • This study was performed using animals to confirm the effect of tourmaline-ionized water (TIW) the properties of which were changed by tourmaline energy and electric discharge. In the ICR mice fed high-fat diet, body weight increasing rate of the TIW-treated group (Exp) was generally decreased and moreover exhibited significance at 11th week (P<0.05) compared with the control (Con) group fed distilled water, although water intake of the Exp group was lower than that of the Con group. In the ICR mice with $CCl_4$-induced hepatotoxicity, AST and ALT activities of the Exp group were not significant but showed some decreasing trend, and histological damage of liver was less compared with thatof the Con group. On the study of ethanol-induced hangovers in Sprague-Dawley rat, blood alcohol concentration was significantly decreased (P<0.01), activity of GST, antioxidant enzyme related to the alcohol metabolism, was increased in liver tissue (P<0.05), and AST and ALT show a tendency to be decreasedin the Exp group. These results suggest that drinking TIWhas not only some obesity preventing effect but also an alcohol detoxification effect and liver protecting effect in vivo. It is supposed due to a structural change of water cluster and a property which maintains the changed structure through tourmaline energy and electric discharge. Therefore, TIW has a potentiality to be developed as functional water with several beneficial effects as well as for daily drinking, but further study on the mechanism related with efficacy will be necessary.