• Title/Summary/Keyword: rat hepatotoxicity

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Hepatoprotective Activity of Bacopa monniera on D-galactosamine Induced Hepatotoxicity in Rats

  • Ramakrishnan, S.;Sumathi, T.
    • Natural Product Sciences
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    • v.13 no.3
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    • pp.195-198
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    • 2007
  • Hepatoprotective action of alcoholic extract of Bacopa monniera (BME) was evaluated on Dgalactosamine (D-GalN) induced rat liver toxicity. Bacopa monniera extract reduced the elevated serum enzyme activities of ALT, AST, ALP, LDH, ${\gamma}-GT$ and the formation of hepatic malondialdehyde induced by D-GalN. The alcholic extract of Bacopa monniera also significantly restored the decreased levels of glutathione and the decreased activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and glucose-6-phosphatase. Therefore these results suggest that Bacopa monniera has hepatoprotective effect against D-GalN induced hepatotoxicity.

The Hepatotoxicity and the Effect of Antioxidative Vitamins by the Simultaneous Administration of Caffeine and Acetaminophen in vitro (Caffeine과 Acetaminophen으로 인한 간독성과 항산화성 비타민의 효과)

  • 노숙령;옥현이;이재관
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.6
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    • pp.1173-1180
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    • 1997
  • Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

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Effects of Keonbodan (健步丹) on MIA-Induced Osteoarthritis in Rat (건보단(健步丹)이 MIA로 유도된 골관절염 Rat에 미치는 영향)

  • Lee, Eun-Jung;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.2
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    • pp.51-64
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    • 2014
  • Objectives This study was carried out to know the effects of Keonbodan (hereinafter referred to KBD) in osteoarthritis induced by Monosodium iodoacetate(hereinafter referred to MIA) on Wistar rat. Methods Osteoarthritis was induced by injection of MIA into left knee joint cavities of rat. Osteoarthritis rats were divided into 4 groups (normal (n=6), control (n=6), indomethacin (n=6), KBD (n=6) group). The control group was administered normal saline and indomethacin group was administered indomethacin (2 mg/kg). And the KBD group was administered KBD (142 mg/kg). Each groups were administered by orally for 4 weeks. This experiment were carried out in vivo. In vivo, at the end of the experiment (5 weeks after MIA injection), effects on hepatotoxicity and nephrotoxicity, cytokines in serum, arachidonic acid, osteocalcin, MMP-9, TIMP-1 and cartilage volume were evaluated. And histopathological examinations on the articular structures of knee joints were performed. Results 1. In weight-bearing measurement, level of weight was increased. 2. In order to hepatotoxicity and nephrotoxicity, ALT, AST, BUN and creatinine were tested. And there were no significant changes. 3. In serum, levels of TNF-$\alpha$, IL-$1{\beta}$ were significantly decreased. IL-6 was insignificantly decreased. 4. In serum, level of MMP-9 and TIMP-1 was decreased. 5. In serum, level of $LTB_4$, $PGE_2$ and osteocalcin was decreased. 6. In ${\mu}$CT-arthrography, the cartilage volume was greater than that of the control group. 7. The joint damage induced by osteoarthritis was lesser than the control group in histopathologic observation (H&E, Safranin-O staining). Conclusions These results demonstrated that KBD suppressed the osteoarthritis- inducing effects of MIA in rat. And further studies are required to find out more effective substance and anti-osteoarthritic mechanism in the future.

The Beneficial Effect of Melatonin for Toluene Hepatotoxicity in Rats

  • Bae, Si-Woo;Yoon, In-Sook
    • Biomedical Science Letters
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    • v.7 no.3
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    • pp.99-102
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    • 2001
  • Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

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Taraxacum Mongolicum H. Suppress Hepatoprotective Activity by Increasing Liver Antioxidant Enzyme in Carbon Tetrachloride($CCl_4$)-induced Hepatotoxicity in Rats (흰쥐에서 민들레 추출물이 사염화탄소에 의한 산화적 스트레스의 경감기전)

  • Kim, Sung-Hoon;Choi, Jong-Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.3
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    • pp.439-445
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    • 2010
  • Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.

Alcoholic Hepatotoxicity Suppression in Alcohol Fed Rats by Glutathione-enriched Yeast FF-8 Strain

  • Cha, Jae-Young;Kim, Hyeong-Soo;Kang, Sun-Chul;Cho, Young-Su
    • Food Science and Biotechnology
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    • v.18 no.6
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    • pp.1411-1416
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    • 2009
  • The suppressive effects of glutathione-enriched Saccharomyces cerevisiae FF-8 strain (FF-8 GY) on alcoholinduced hepatotoxicity have been studied. FF-8 GY (256 mg/L) from the fermentation at a large scale bioreactor was used. Either of 5% FF-8 GY or 5% commercial glutathione-enriched yeast extract (GYE) with or without 30% alcohol was tested with rats for 4 weeks. FF-8 GY and GYE were found to reduce those alcohol-elevated serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities. Blood alcohol and acetaldehyde were also decreased by FF-8 GY and GYE. Interestingly, FF-8 GY drastically increased both hepatic alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities in comparison to GYE group, thus FF-8 GY would be more effective in blood alcohol and acetaldehyde reduction. Attenuated lipid droplet accumulation in hepatocytes was observed in both FF-8 GY and GYE when alcohol stimulated the accumulation. Therefore, FF-8 GY may be useful to protect liver from alcohol-induced hepatotoxicity.

MICROCIRCULATORY ABERRATIONS IN THE ISOLATED PERFUSED RAT LIVER INDUCED BY SODIUM CYANIDE, ANOXIA OR ACETAMINOPHEN

  • Jung, Kihwa
    • Toxicological Research
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    • v.5 no.1
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    • pp.27-35
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    • 1989
  • When acetaminophen (25mM) was introduced into the perfused rat liver, the hepatic O2 uptake was rapidly inhibited first and then later slow-down. The rapid inhibition was found to be due to mitochondrial blockade, whereas the so-called slow inhibition" was associated with microcirulatory aberrations as evidenced by inhomogneous staining of the liver tissue by trypan blue infusion (0.1%). NaCN (0.5mM) also caused rapid and slow respiratory inhibitions, giving heterogeneous trypan blue staining.ning.

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The Preventive Effects of Standardized Extract of Zataria multiflora and Carvacrol on Acetaminophen-Induced Hepatotoxicity in Rat - Zataria multiflora and Carvacrol and Hepatotoxicity -

  • Mohebbati, Reza;Paseban, Maryam;Beheshti, Farimah;Soukhtanloo, Mohammad;Shafei, Mohammad Naser;Rakhshandeh, Hasan;Rad, Abolfazl Khajavi
    • Journal of Pharmacopuncture
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    • v.21 no.4
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    • pp.249-257
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    • 2018
  • Objectives: The hepatotoxicity induced by Acetaminophen (AAP) mostly mediated by effect on oxidative stress parameters. The Zataria multiflora (Z.M) is an herbal medicine with well-known antioxidant effect. The aim of this study is investigation of preventive effects of Z.M and Carvacrol (CAR) on AAP-induced hepatotoxicity in rats. Methods: Rats were randomly divided into four groups including: 1) Control, 2) Acetaminophen (AAP), 3) and 4) CAR. The saline, Z.M (200 mg/kg) and CAR (20 mg/kg) were administrated orally for 6 days, after that AAP (600 mg/kg) was administrated in the $7^{th}$ day. Blood sampling was performed on the first and last days. Also, the liver tissue was removed for evaluation of Malondyaldehide (MDA), Thiol content, Superoxide dismutase (SOD) and Catalase (CAT). Total Protein (tPro), Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP) in liver tissue were evaluated. The changes (${\Delta}$) of enzymes activities were presented. Results: The ${\Delta}GOT$, ${\Delta}GPT$ and ${\Delta}ALP$ in CAR group significantly decreased compared to AAP group (P < 0.01 to P < 0.001) and ${\Delta}GPT$ in Z.M group was significantly reduced in comparison with AAP group (P < 0.05). Also, MDA, Thiol, SOD and CAT levels in treated groups were attenuated compared to AAP group (P < 0.05 to P < 0.001). Conclusion: Z.M and CAR have a powerful hepatoprotective effect. CAR is more effective than Z.M. Based on the results. Z.M and CAR could be potent supplementary agents against hepatotoxicity of AAP in patients.

Effects of Ethanol Extract of Prunus mume on the Antioxidative System and Lipid Peroxidation on Ethanol-Induced Hepatotoxicity in Rat Liver (매실 추출물이 알코올 투여 흰쥐의 항산화계 및 지질과산화에 미치는 영향)

  • 이정현;나명순;이명렬
    • Food Science and Preservation
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    • v.11 no.1
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    • pp.71-78
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    • 2004
  • To investigate the antioxidative effects of Prunus mume ethanol extract on the ethanol-induced hepatotoxicity in rat liver, Sprague-Dawley rats weighing 120∼160 g were divided into 5 groups; normal group(NOR), Prunus mume ethanol extract 200mg/kg treated group(PME), ethanol(10 mL/kg, 35%) treated group(ETH), Prunus mume ethanol extract 200 mg/kg and ethanol treated group (PML) and Prunus mume ethanol extract 400 mg/kg, and ethanol treated group(PMF), respectively. The antioxidative activity in vitro was reduced in order of EtOAC>n-hexane>water> chloroform fraction. The growth rate and feed efficiency ratio decreased by ethanol administration were gradually increased to the adjacent level of NOR by administering Prunus mume ethanol extract. It was observed that activities of catalase, superoxide dismutase(SOD), xanthine oxidase and glutathione peroxidase(GSH-Px) of liver and alanine aminotransferase(ALT) and asparate aminotransferase(AST) of serum were elevated by ethanol administration. Besides, Prunus mume ethanol extract markedly decreased elevated activites of catalase, GSH-Px, ALT and AST, except in activites of SOD and xanthine oxidase compared to ETH. Also, the depleted content of GSH by ethanol was increased similar to NOR level by administering Prunus mume ethanol extract. These results suggested that Prunus mume ethanol extract has a possible protective effect on the ethanol-induced hepatotoxicity in rat liver.

Protective Effects of the Water Extracts of Hovenia dulcis Thunb Against Ethanol-Induced Toxicity in Primary Cultured Rat Hepatocytes (랫드 일차 배양 간세포에서 에탄올의 독성에 대한 헛개나무 물추출물의 보호효과)

  • Kim, Jong-Ho;Seo, Young-Min;Kim, Ju-Hyun;Hyun, Sun-Hee;Lee, Sang-Kyu;Kim, Chun-Hwa;Kang, Mi-Jeong;Jeon, Tae-Won;Yoon, Soo-Hong;Jeong, Tae-Cheon
    • YAKHAK HOEJI
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    • v.52 no.1
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    • pp.56-61
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    • 2008
  • The hepatoprotective effects of the water extracts of Hovenia dulcis Thunb (HD) were investigated in vitro. Following the induction of hepatotoxicity by ethanol in primary cultures of rat hepatocytes, the protective effects of four different water extracts of HD were determined through serial dose-response and time-dependent studies. The individual extracts used in these studies were prepared from fruits, seeds, leaves and tubes. Treatment of hepatocyte cultures with the water extracts of HD provided a significant protection from the increased lactate dehydrogenase activity induced by ethanol. Particularly, the fruits extract was the most effective against ethanol-induced hepatotoxicity in the primary cultures of rat hepatocytes. The results demonstrated that the extracts might have the protective effect against ethanol-induced toxicity in hepatocyte cultures.