• Title/Summary/Keyword: hepatic toxicity

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A Toxicological Study of Young Fronds of Bracken Fern (Pteridium aquilinum var latiusculum) Collected in Kwang Ju Area (한국산 고사리의 독성조사에 관한 연구)

  • Sheo, Hwa-Joong;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.18 no.3
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    • pp.255-264
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    • 1989
  • The results of toxicity test using mice and rats for ethanol extract of Bracken Fern collected in Kwang Ju area were shown as follows ; Up to the dose of 10g per kg of mice administered intraperitoneally there was no lethal toxicity so that it was impossible to calculate the median lethal dose $(LD_{50})$. For the first 7 days experiment all rats administered frond extract grouping in 40mg, 400mg, and 1200mg per kg of rat as the daily oral doses did not show any characterized sign in the weight gain rate, anatomical findings, and biochemical studies. For 3 weeks following the first week the weight gain rates of all test group were reduced to $4.2{\sim}7%$ below the weight gain rate of control. In this period serum GPT, GOT, and Alkaline phosphatase value were increased significantly indicating the symptoms of Bracken Fern poisonings. The pathological findings of all test groups for 28 days showed acute and chronic intestinal lesion and liver damage with steatosis especially in 1200g/kg rat groups. In this experiment the Bracken poisonings appeared slowly in rats of 400mg/kg and 1200mg/kg for two weeks and in rats of 40mg/kg for 3 weeks, showing the symptoms of lowering of weight gain rate, subacute hepatitis, hepatic steatosis and enteritis in 28 days experiment.

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A Study on Accumulation of Cadmium and Induction of Metallothionein in Organs of Rats by Cadmium and Zinc (카드뮴 및 아연투여에 의한 흰쥐의 장기내 Cadmium 축적 및 Metallothionein 생성변화)

  • 이재형;김정현;김남송;김준현;기노석
    • Journal of Environmental Health Sciences
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    • v.20 no.2
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    • pp.64-72
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    • 1994
  • Tolerance to toxic effects of cadmium (Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 108 rats, were studied and each group was divided into three subgroups (1, 2, 3), 12 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl$_2$ (0.5 mg/kg, B), and ZnCl$_2$ (13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with CdCIa (3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggests that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretteatmerit, served to induced the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

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Inhibitory Effect of Hizikia fusiformis Solvent-Partitioned Fractions on Invasion and MMP Activity of HT1080 Human Fibrosarcoma Cells

  • Lee, Seul-Gi;Karadeniz, Fatih;Oh, Jung Hwan;Yu, Ga Hyun;Kong, Chang-Suk
    • Preventive Nutrition and Food Science
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    • v.22 no.3
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    • pp.184-190
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    • 2017
  • Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.

Metronidazole Reduced Ammonia Toxicity in Human Hep G2 cell and Rat Hepatocytes (Hep G2 세포와 rat 간세포에서 Metronidazole에 의한 암모니아 독성 감소)

  • Kim, Bo-Ae;Kim, Hyun-Jung;Kim, You-Young
    • KSBB Journal
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    • v.23 no.5
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    • pp.381-386
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    • 2008
  • Lipophilic ammonia is toxic gas and can easily diffuse across cell membranes. Excess ammonia is implicated in the pathogenesis of several metabolic disorders including hepatic encephalopathy and may result in the death. The purpose of this study was to clarify the inhibition effect of metronidazole on liver cell damage due to ammonia in human Hep G2 cell and rat hepatocytes. The effects of metronidazole were studied in ammonium chloride treated human Hep G2 cell (75 mM) and rat hepatocyte (100 mM) following $0.1{\mu}M$ metronidazole treatment. In MTZ+AC group, cell viabilities increased prominently and LDH activities decreased over 25% than AC group. Furthermore, ammonia level according to ammonium chloride treatment reduced over 30% and lipid peroxidation as an index of cell membrane damage decreased more than twice. By comparison with control, catalase activity showed more than 30% reduction in AC group while less than 10% reduction in MTZ+AC group, respectively. In addition, MTZ+AC group showed the similar cell structure as control in cell morphology study by using light microscope, and represented fluorescent intensity decrement compared with AC group in fluorescent microscopic study with avidin-TRITC fluorescent dye. And cleaved PARP expression due to ammonia reduced twofold or more in MTZ+AC group. As the results suggest, metronidazole may protect the liver cell by inhibiting cell damages due to ammonia and be used for an effective antagonist of ammonia in hyperammonemia.

Effects of Squalene on the Mice Hepatotoxicity Induced by Lead Acetate (납으로 유발된 생쥐 간장 독성에 대한 스쿠알렌의 효과)

  • Kim, Jong-Se
    • Applied Microscopy
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    • v.33 no.3
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    • pp.205-214
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    • 2003
  • To investigate the effect of the squalene against the lead toxicity. A healthy male of ICR mice were used for experiment. The SOD was observed after the intraperitoneal injection in mice. The ultrastructural changes of the liver were observed after the intraperitoneal injection in mice. The experimental groups were divided into two groups. Group A was control group that squalene was not treated after intraperitoneal injection of lead acetate. Group B was squalene treatment group that squalene solution was injected after intraperitoneal injection of lead acetate. All groups were used to 10 mice. The results were as follow: SOD activity in the liver, Group A was lower than in normal. But, Group B was higher than in Group A (P<0.05). In the histological observation, Group A were showed that the inner cavity of mitochondria swellen and development of cristae weakened. Swelling of lamellae of rough endoplasmic reticulum (rER) was showed. It was concluded that the SQ will be effective for the recovery of hepatic cell at lead intoxication.

Protective Effects of near nile Juice Against Carbon Tetrachloride-Induced Acute Hepatotoxicity in ICR Mice (웅담이 CCl4로 유발된 mouse의 간 손상에 미치는 영향)

  • Kim, Hyun-Do;Lee, Kyu-Jae;Park, Seong-Kyu;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.8 no.3
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    • pp.31-38
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    • 2005
  • Objectives : This study was aimed at investigating liver protection mechanism of bear bile juice (Fel Ursi)by inducing liver toxicity through $CCl_4$ in mice and evaluated histological and serological findings. Methods : Experiment groups was categorized into untreated normal group, $CCl_4$ treated control group, and orally administered bear bile juice experiment group. At the termination of experiment, gross examination of the liver as well as histological findings, and Total protein, Albumin, Total bilirubin, Direct bilirubin SGOT, SGPT, and ALP contents in the serum were evaluated. Results : 1. For gross examination and histological findings, $CCI_4$ treated control group showed destroyed lobular structure, increased fibrosis, as well as hepatic cirrhosis. For the group treated with bear bile juice, the lobular structure suffered less damage, and showed lower level of fibrosis and liver cirrhosis compared to the control group. 2. For serum analysis, Total protein and Albumin were significantly increased in the bear bile juice experiment group than the control group. Total bilirubin and Direct bilirubin didn't show significant differences between the two groups. SOOT, SGPT, and ALP were significantly decreased in the normal and bear bile juice experiment groups compared to the control group. Conclusion : Taken together, bear bile juice can be effectively used for recovering the liver functions and further researches must be conducted to verify the efficacies of bear bile juice.

Protective Effects of Moschus Against Carbon Tetrachloride-Induced Acute Hepatotoxicity in ICR Mice (사향이 CCl4로 유발된 mouse의 간 손상에 미치는 영향)

  • Park, Jae-Seuk;Kim, Seung-Wook;Lee, Kyu-Jae;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.9 no.1
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    • pp.45-52
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    • 2006
  • Objectives : This study was aimed at investigating liver protection mechanism of Moschus by inducing liver toxicity through $CCl_4$ in mice and evaluated histological and serological findings. Methods : Experiment groups was categorized into untreated normal group, $CCl_4$ treated control group, and orally administered Moschus experiment group. At the termination of experiment, gross examination of the liver as well as histological findings, and Total protein, Total bilirubin, Direct bilirubin SGOT, SGPT, and ALP contents in the serum were evaluated. Results : 1. For gross examination and histological findings, $CCl_4$ treated control group showed destroyed lobular structure, increased fibrosis, as well as hepatic cirrhosis. For the group treated with Moschus, the lobular structure suffered less damage, and showed lower level of fibrosis and liver cirrhosis compared to the control group. 2. For serum analysis, Total protein were significantly increased in the Moschus experiment group than the control group. 3. Total bilirubin didn't show significant differences between the two groups. but direct bilirubin was significantly increased in the Moschus experiment group than the control group. 4. SGOT, SGPT, were significantly decreased in the normal and Moschus experiment groups compared to the control group. 5. ALP was significantly decreased in the normal group compared to the control group, but Moschus experiment group didn't show significant differences compared to the control group. Conclusion : Taken together, Moschus can be effectively used for recovering the liver functions and further researches must be conducted to verify the efficacies of Moschus bile juice.

The Effect of Autoxidized Methyl Linoleate on the Lipid Metabolism in the Mouse (Chronic Toxicity) (자동산화 Methyl Linoleate가 Mouse의 지질대사에 미치는 영향(만성독성))

  • Paik, Tai-Hong;Lee, Keun-Hwan
    • Journal of the Korean Applied Science and Technology
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    • v.3 no.2
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    • pp.35-40
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    • 1986
  • In order to investigate the effect of autoxidized methyl linoleate (AOML) on the lipid metabolism in the mouse, we administered the fixed dosage of AOML to mice onece per day for 20 days by using stomach tube. And the following results were obstained. The amounts of triglycerides, phospholipids, total cholesterol and TBA values in the blood serum of test group were increased more than these of normal group. And according to the electrophoresis, the amount of albumin in test group was increased about 22% in comparision with normal group but the amount of VLDL and LDL was decreased about 70% and 30% respectively. The POV, COV and TBA values in the liver of test group were significantly increased more than these in normal group. And also the amounts of triglycerides, phospholipids and total cholesterol in test group were slightly increased. And the damage of hepatic cells and the accumulation of fats were observed as the morphorogical changes in the liver of test group. Form these results obtained, we conclude that the autoxidized methyl linoleate fed in mice influences at lipid metabolism on the blood and the liver.

Effects of Natural Products on the Induction of NAD(P)H: Quinone Reductase in Hepa 1c1c7 Cells for the Development of Cancer Chemopreventive Agents

  • Kim, Young-Mi;Chang, Il-Moo;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.3 no.2
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    • pp.81-88
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    • 1997
  • NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

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Study on pharmacological activities of the roots of Cicorium intibus

  • Yim, Dong-sool;Kim, Kwang-sub;Cheong, Jae-hoon;Lee, Sook-yeun
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.74-74
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    • 1997
  • Chicory is used popularly. We use leaves of the plant as ordinary mea1, and roots as a substitute of tea materials. It also has been asserted that it has clinical effects on weakness, hepatic disease, diabetes, etc. However, experimental evidences are so insufficient that we started these studies. For antiinflammatory activity, MeOH Ex. was orally administered to rats, and decreased amounts of paw edema induced by carrageenan injection were measured. For bile secretion increament, rats were administered total MeOH, EtOAc fraction, and BuOH fraction Ex. respectively. One hour later, bile ducts were cannulated, and we collected bile every 20 minutes for 4 hours. For hepatoprotective activity, CCl$_4$-intoxicated mouse were treated with MeOH Ex., then s-GPT, S-GOT, and liver weight were measured. For antidiabetic activity, rats were induced diabetes by streptozocin 45mg/kg(i.v) injection. One week later, 1000mg/kg of total MeOH Ex. of chicory root was orally administered. We divided rats into three groups. Group 1 rats were administered only once, group 2 ones once a day for one week, and group 3 ones for three weeks. The concentrations of serum glucose were measured before and after administration. For antihypertensive activity, SHR were administrated total MeOH Ex. of chicory once a day for 8 days, and were measured blood pressure on 1st, 3rd, 6th and 8th day. Total MeOH, EtOAc fraction, and BuOH fraction Ex. increased bile secretion in rats, and decreased liver toxicity induced by CCl$_4$ in mouse. Total MeOH, Ex. of chicory roots has antiinflammatory effect, and decreased blood glucose concentration in group 2 and 3 rats. It was revealed not lowering blood pressure significantly in SHR.

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