• Title/Summary/Keyword: Liver dose

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Oral Repeated-dose Toxicity Studies Especially in the Liver and Kidney of Rats Administered with Organic Germanium-fortified Yeasts

  • Lee, Sung-Hee;Oh, Kyeong-Nam;Rho, Sook-Nyung;Lee, Bok-Hee;Lee, Hyun-Joo
    • Preventive Nutrition and Food Science
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    • v.11 no.2
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    • pp.115-119
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    • 2006
  • The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

Protective Effects of Sasa borealis Bamboo Browse Extract on Acetaminophen-induced Liver Damage in Mouse Model (Acetaminophen 유도 간 손상에 대한 조릿대 애엽 추출물의 보호 효과)

  • Jang, Seon-Il;Yun, Young-Gab;Park, Kwang-Hyun;Xie, Guanghua;Kwon, Tae-Oh
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.183-191
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    • 2008
  • Acetaminophen (N-acety1-p-aminophenol, paracetamol) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a over dose of acetaminophen may result in severe hepatic necrosis. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of acetaminophen and the possible protective effects of administration (50-200 mg/kg body weight) of SB-Ex on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of SB-Ex on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase (${\sigma}$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. Acetaminophen caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, catalase, ${\sigma}$-ALA-D, and GPx and an increase in TBARS in the liver of acetaminophen-treated group compared with the control group. However, SB-Ex was able to counteract these effects. These results suggest that SB-Ex can act as hepatoprotectives against acetaminophen toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

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Effects of Larval Extracts from P. brevitarsis seulensison Cytokine and Diagnostic Marker in Carbon Tetrachloride-Administered SD Rats

  • Lee, Ji-Sook;Kwon, Ohseok;Hwang, Seock-Yeon;Yun, Chi-Young
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.3
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    • pp.113-119
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    • 2011
  • This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

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Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine/lipopolysaccharide-induced liver injury model in rats

  • Nam, Yoonjin;Bae, Jinhyung;Jeong, Ji Hoon;Ko, Sung Kwon;Sohn, Uy Dong
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.540-548
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    • 2018
  • Background: Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods: Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results: After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion: UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.

Healing and preventive effects of low-esterified pectin on liver injury induced by carbon tetrachloride in rats

  • Khotimchenko, Yuri S.;Kolenchenko, Elena A.;Khotimchenko, Maxim Y.;Kovalev, Valeri V.
    • Advances in Traditional Medicine
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    • v.4 no.1
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    • pp.28-36
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    • 2004
  • The purpose of this study was to investigate the pharmacological effects of low-esterified pectin on carbon tetrachloride $(CCL_4)-induced$ hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily $CCL_4$ through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of pectin for 21 days. At the end of experiment rats were killed within 24 hours. The increased bilirubin level, enhanced alanine aminotransferase and aspartate aminotransferase activity in plasma induced by $CCL_4$ were partly normalized by pectin administration in a dose-dependent manner. The pectin treatment also resulted in significant recovery of $CCL_4-induced$ decrease of the liver glycogen content. In addition, pectin significantly improved $CCL_4-induced$ alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered $CCL_4$. In the second experiment the animals were given daily 10, 50 or 250 mg/ kg b.w. of pectin for 21 days before a 7-day administration of $CCL_4$. Rats were killed 24 hours after the end of experiment. Pretreatment with pectin before $CCL_4$ administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of pectin prevented elevation of malondialdehyde and conjugated diene levels in liver and plasma as well as a reduction of glutathione content in liver of rats given $CCL_4$. These results suggest that low-esterified pectin exert healing and preventive effects on $CCL_4-induced$ hepatotoxicity in rats.

Effect of TJGB on the liver of high-fat diet-fed mice and the viability of HepG2 cells (고지방식이를 급여한 마우스의 간과 HepG2 세포에서 TJGB의 효과에 대한 연구)

  • Hee-Young Kim;Yea-Jin Park;Hyo-Jin An
    • Journal of Convergence Korean Medicine
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    • v.5 no.1
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    • pp.55-60
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    • 2023
  • Objectives: This study was performed to investigate the effect of TJGB on the liver of high-fat diet (HFD)-fed mice and the cell viability of HepG2 cells. Methods: After a week adaptation, 8-week-old C57BL/6N mice were fed with a 45% HFD or normal diet for 3 weeks. For the next 9 weeks, the mice were divided into 6 groups: normal diet group; HFD group; HFD plus orlistat group; HFD plus Ephedra sinica Stapf (ES) group; HFD plus low dose of TJGB group; HFD plus high dose of TJGB group. To estimate the effect of TJGB in the liver of HFD-fed mice, the protein expressions of phospho-acetyl-CoA carboxylase (p-ACC) and liver X Receptor (LXR) were determined by Western blot assay. The cell viability of ES and TJG was also evaluated in HepG2 cells. Results: The administration of TJGB had little effect on the protein expressions of p-ACC and LXR in the liver of HFD-fed mice. And the cytotoxicity was showed above 7.8 ㎍/mL in HepG2 cells. Conclusion: Further research is needed to evaluate the mechanism of TJGB on hepatic steatosis and cytotoxicity in HepG2 cells.

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Protective effects of Paeoniae Radix Alba and Puerariae Radix combination on alcoholic liver disease (알코올성 간 손상 동물 모델에서 芍藥 葛根 복합물의 간 손상 보호 효과)

  • Jeong Won, Choi;Jin Young, Kim;Mi-Rae, Shin;Hae-Jin, Park
    • The Korea Journal of Herbology
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    • v.38 no.1
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    • pp.31-43
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    • 2023
  • Objective : Alcoholic liver disease (ALD) is caused by excess alcohol intake. In the liver, alcohol breakdown results formation of toxic byproducts that lead to damage to tissue. This study is to investigate the therapeutic effects of Paeoniae Radix Alba and Puerariae Radix combination (PP) on ALD. Methods : PP was analyzed for polyphenolic compounds and free radical scavenging activity. ALD mouse model was induced by feeding ethanol and water (Control), silymarin (50 mg/kg), low-dose (PP: 100 mg/kg) or high-dose (PP: 200 mg/kg) was orally administrated to ALD mice for 14 days. The serum was assessed with levels of AST, ALT, total bilirubin, total cholesterol, and triglyceride. Liver tissues were evaluated for ROS levels, degree of liver damage and protein expression. Results : The 3:1 (Paeoniae Radix Alba:Puerariae Radix) ratio showed the best antioxidant values for the experiment. In ALD model, levels of AST, ALT, total bilirubin, total cholesterol, and triglyceride were significantly increased in the Control and the levels were decreased by treatment of PP. In addition, increased ROS, ONOO- and MDA levels in the Control were reduced in the PP groups. Western blot analysis figured out that proteins related to ROS and cholesterol metabolism were higher in ALD than in PP-treated ALD. Antioxidant enzyme expression was low in the control group and increased by PP treatment. Conclusion : Our results suggest that PP has the potential to be a medicine in ALD in terms of regulating oxidative stress and adjusting lipid metabolism.

Effect of combination treatment of vitamin E and insulin in streptozotocin-treated rats and BB rats I. Effect on the oxidative modification of lipid and protein, and enzyme activitis (BB 랫드 및 streptozotocin이 투여된 랫드에서 vitamin E와 insulin 병합 투여 영향 I. 지질과 단백질의 산화성 손상 및 혈청내 효소 활성도에 미치는 영향)

  • Kim, Soon-tae;Huh, Rhin-sou
    • Korean Journal of Veterinary Research
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    • v.35 no.4
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    • pp.699-712
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    • 1995
  • The present study, to evaluate the effect of vitamin E on the oxidative stress in STZ-treated rat and BB rat, was investigated the biochemical enzyme activity in the serum, and malondialdehyde and carbonyl group in the RBC membrane, liver and microsomal fraction after vitamin E and/ or insulin treatment. Results obtained through the experiments were summarized as follows; 1. Effect of vitamin E and/or insulin treatment in STZ-treated rat 1) Lipid peroxidation level in RBC membrane, liver and microsomal fraction was significantly decreased in vi. tamin E and/or insulin treatment group, and especially more significantly decreased in vitamin E with insulin treated group. 2) Protein oxidation level in RBC membrane, liver and microsomal fraction was significantly decreased in vitamin E and/or insulin treatment group. And it was especially more significantly decreased in RBC membrane and liver of vitamin E with insulin treated group. 3) In the enzyme activity in the serum, the activity of AST and ALT was not altered in all experimental group. The increased ALP activity in STZ-treated group was significantly decreased in insulin treated group and vitamin E with insulin treated group. 4) Decreased level of albumin and creatinine after STZ treatment was significantly increased in vitamin E and/or insulin treated group. 5) Level of glucose, cholesterol and triacylglycerol in serum: Glucose level was not significantly different in vitamin E treated group compared to STZ control group. But it was significantly different in the insulin treated group and vitamin E with insulin treated group compared to STZ control group. The cholesterol content in the serum was significantly increased in STZ control group compared to normal control group. And except low dose vitamin E treatment group, it was significantly decreased in vitamin E and/or insulin treated group compared to STZ control group. The triacylglycerol content in the serum was significantly decreased in STZ control group and increased in high dose vitamin E treated group and vitamin E with insulin treated group. But it was not significantly different in low dose vitamin E treated group and insulin treated group compared to STZ control group. 2. Effect of vitamin E and/or insulin treatment in BB rat 1) Lipid peroxidation level in liver was decreased by vitamin E with insulin treatment compared to insulin treatment. But it was not different in microsomal fractions. 2) Protein oxidation level in liver and microsomal fraction was decreased by vitamin E with insulin treatment compared to insulin treatment only in microsomal fractions. These results suggest that the combination treatment of vitamin E and insulin could prevent the oxidative change of lipid and protein of the RBC membrane, liver and microsomal fraction in STZ-treated rats and BB rats.

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The Effects of Ka-Mi-Chung-Gan-Tang on Rat with Alcoholic Fatty Liver (가미청간탕(加味淸肝場)이 Rat의 알콜성 지방간에 미치는 영향)

  • Zheng, Cheng-Xuan;Yim, Dong-Sool;Lee, Sook-Yeon
    • Korean Journal of Pharmacognosy
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    • v.35 no.3 s.138
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    • pp.229-232
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    • 2004
  • Chronical intake of alcohol can cause alcoholic fatty liver. Fatty liver is caused by fat infiltration: the state of high rate of fat in liver cells and by losing the balance between the synthesis and the secretion of fatty acid. It could be developed into liver necrosis and cirrhosis. Ka-Mi-Chung-Gan-Tang (KMCGT) is a decoction used for fatty liver as oriental medicines in China. The prescription is composed of Ginseng Radix, Bupleuri Radix, Scutellariae Radix, Pinelliae Tuber, Artemisiae capillaris Herba, Gardeniae Fructus, Zingiberis Rhizoma, Zizyphi Fructus and Glycyrrhizae Radix etc. We have induced alcoholic fatty liver by ethanol administration (6 g/kg, single dose/day, for a week) on rats and observed changes of triglyceride, cholesterol and lipid peroxidation in liver tissues of them. Also we checked the activities of GOT and GPT in blood of rats. KMCGT inhibited significantly the increase of triglyceride, cholesterol, lipid peroxidation level and effectively the increase of malondialdehyde (MDA).

The Experimental Study on Biochemical Changes of Rat Liver Following Single Irradiation of High Energy X-ray (고(高)에너지 방사선(放射線)을 1회조사(一回照射)한 흰쥐 간(肝)의 생화학적(生化學的) 변화(變化))

  • Lee, Joon-Il;Park, Myeong-Hwan;Park, Chong-Sam
    • Journal of radiological science and technology
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    • v.16 no.2
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    • pp.87-94
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    • 1993
  • In order to investigate radiation effects on the liver, functional changes of liver were analyzed after irradiation. Doses of 10 Gy, 15 Gy and 20 Gy were exposed partially to the liver of male rats(Sprague-Dawley) with X-ray(4MV linear accelerator) at room temperature. On 1, 2, 4 and 8 weeks after irradiation, liver tissues and sera of the animals were compared with those of unirradiated animal by liver function tests. Enzyme activities in sera such as alanine aminotransferase, aspartate aminotransferase, malondialdehyde. The content of malondialdehyde in the activities of many enzymes including alanine aminotransferase, aspartate aminotransferase in sera were increased slightly with increasing exposure dose in all experiments and the activities of these enzymes increased markedly in 20 Gy irradiated groups. From these above results, functional changes of the liver were induced in all irradiated groups. Damaged liver was recovered along with time collapse after irradiation to the doses of 10 Gy and 15 Gy while no recovery was deteced within 8 weeks after irradiation to 20 Gy. These results suggest that careful attention must be paid to liver not to be included in exposure field in radiation therapy.

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