• Title/Summary/Keyword: hepatic glutathione

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Hepatotoxic Effect of 1-Bromopropane and Its Conjugation with Glutathione in Male ICR Mice

  • Lee Sang Kyu;Jo Sang Wook;Jeon Tae Won;Jun In Hye;Jin Chun Hua;Kim Ghee Hwan;Lee Dong Ju;Kim Tae-Oh;Lee Eung-Seok;Jeong Tae Cheon
    • Archives of Pharmacal Research
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    • v.28 no.10
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    • pp.1177-1182
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    • 2005
  • The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

Effects of Circii Herba Aqua-Acupuncture (BL18, CV12) on Acute Oxidative Liver Injury (간유(肝兪).중완(中脘)의 대계(大?) 약침(藥鍼)이 급성 산화적 간손상에 미치는 효과)

  • Lee Jeong-Joo;Moon Jin-Young
    • Korean Journal of Acupuncture
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    • v.20 no.4
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    • pp.41-52
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    • 2003
  • Objectives : Circii Herba has been used as a natural drug for the treatment of stress digestive system disease. The aim of this study is to investigate the role of Circii Herba aqua-acupuncture solution (CHAS) in experimental oxidative liver injury. Methods : In order to investigate the effects of CHAS on acute liver injury, male ICR mice were pretreated with CHAS(0.2 ml/mouse/day) at the loci of BL18 and CV12 for 6days, starved for 24hrs, and administerated acetaminophen(500 mg/kg, i.p.). After acetaminophen administeration, mice were sacrificed, and the liver was removed, rinsed with ice-cold $1.15{\%}$ KCI buffer, and homogenized at $4^{\circ}C$. Fractions(fraction Ⅰ, Ⅱ, Ⅲ) were isolated by differential centrifugation. Lipidperoxide, total SH, and glutathione(GSH) levels were measured in the Fraction Ⅰ. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px) were measured in the Fraction Ⅱ, and glutathione S-transferase(GST) was measured in the Fraction Ⅲ. Results : In vivo treatment of CHAS(BL18 and CV12) showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of total SH, GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that CHAS might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

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Effect of Taurine Supplementation on Hepatic Lipid Peroxide Metabolism in Streptozotocin-induced Diabetic Rats

  • You, Jeong-Soon;Chang, Kyung-Ja
    • Journal of Community Nutrition
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    • v.2 no.2
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    • pp.164-169
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    • 2000
  • The purpose of this study was to examine the effect of taurine supplementation time on the activity of the enzymes metabolizing lipid peroxide in the liver of streptozotocin(STZ)-induced diabetic rats, Sprague-Dawley male rats were fed the purified diet for 7 weeks. They were supplemented with or without 1% taurine in drinking water before or after STZ injection or during all experimental procedure. In comparison to diabetic group without taurine, glucose-6-phosphatase(G6Pase) activity was decreased in diabetic group supplemented with taurine before STZ injection, and it was increased in diabetic group supplemented with taurine after STZ injection, but the difference was not significant. Glutathione S-transferase(GST) activity was significantly increased by the injection of STZ. However, the GST activities of diabetic groups exposed to taurine after STZ injection or during all experimental procedure were significantly decreased. Glutathione peroxidase(GPx) activities was significantly decreased by STZ injection. However, only in diabetic group supplemented with taurine before STZ injection, GPx activities was not decreased by the STZ injection. These results suggest that taurine supplementation may change the activities of GSH-related enzymes metabolizing lipid peroxide in the liver of streptozotocin(STZ)-induced diabetic rats and that may be helpful for the prevention of diabetic complication.

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Protective Effect of Diallyl Disulfide on the Bromobenzene-Induced Hepatotoxicity in Mice (Bromobenzene 간손상에 대한 Diallyl Disulfide의 예방효과)

  • Lee, Sang-Il;Yoon, Chong-Guk;Huh, Keun
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.185-192
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    • 1990
  • The present work was undertaken to investigate the protective effect of diallyl disulfide on the bromobenzene toxicity in mice. It was observed that the aniline hydroxylase and epoxide hydrolase activities were not changed by the treatment of diallyl disulfide for 5 days. But glutathione S-transferase activity was significantly increased. A striking enhancement of serum alanine aminotransferase activity and hepatic lipid peroxide content after bromobenzene administration was markedly decreased by diallyl disulfide pretreatment. These results indicate that the inducing effects of diallyl disulfide on the bromobenzene intermediate detoxifying enzyme such as glutathione S-transferase are believed to be a possible protective mechanism for the bromobenzene toxicity in mice.

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Protective Effect of Administrated Glutathione-enriched Saccharomyces cerevisiae FF-8 Against Carbon Tetrachloride ($CCl_4$)-induced Hepatotoxicity and Oxidative Stress in Rats

  • Shon, Mi-Yae;Cha, Jae-Young;Lee, Chi-Hyeoung;Park, Sang-Hyun;Cho, Young-Su
    • Food Science and Biotechnology
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    • v.16 no.6
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    • pp.967-974
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    • 2007
  • The present work is aimed to evaluate the protective effect of glutathione-enriched Saccharomyces cerevisiae FF-8 strain on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and oxidative stress in rats. The activities of liver markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase), lipid peroxidative index (thiobarbituric acid-reactive substances), and the antioxidant status (reduced glutathione) were used to monitor those protective roles of FF-8 strain. The liver marker enzymes in plasma and the lipid peroxidation in the liver were increased when $CCl_4$ was treated but these were significantly decreased by FF-8 strain treatment. The hepatic concentration of glutathione in the current glutathione-enriched FF-8 strain fed animal was approximately twice as high as the normal, but this was slightly increased in response to $CCl_4$ plus glutathione-enriched FF-8 strain. The increased liver triglyceride concentration due to the $CCl_4$ treatment was significantly decreased by FF-8 strain and the reduced level reached to that of normal group. Administration of FF-8 strain in normal rat did not show any signs of harmful effects. Therefore, the current findings suggest that FF-8 strain could be an effective antioxidant with no or negligible side-effects and it might be useful for the purpose of protection treatment of hepatotoxicity and oxidative stress in $CCl_4$-treatment in rat.

Effects of Green Tea Extract on Acute Ethanol-induced Hepatotoxicity in Rats (녹차추출물이 에탄올 투여에 의한 초기 간 손상에 미치는 영향)

  • Jin, Dong-Chun;Jeong, Seung-Wook;Park, Pyoung-Sim
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.3
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    • pp.343-349
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    • 2010
  • The liver is the major target of ethanol toxicity and oxidative stress plays a role in development of alcoholic liver disease. This study was performed to investigate the effects of green tea extracts (GTE) on acute ethanol-induced hepatotoxicity in rats. Experimental animals were divided into 4 groups, control, GTE, ethanol, and GTE+ethanol treatment, with 5 rats in each group. Ethanol (6 g/kg body weight (BW)) and GTE (200 mg/kg BW) were treated by gavage. At 1 hour, 3 hours and 20 days (6 g/kg BW every 2 days for total 10 doses) after ethanol and/or GTE treatments, animals were killed; hepatic tumor necrosis factor-alpha (TNF-$\alpha$) and glutathione level, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), hepatic antioxidant enzymes (SOD, CAT, GPx) activities and hepatic thiobarbituric acid reactive substances (TBARS) were measured. At 1 hour and 3 hours, hepatic TNF-$\alpha$ levels were increased significantly in ethanol group and ethanol+GTE group but that levels was significantly lower in ethanol+GTE group compared with ethanol group. Hepatic glutathione level was decreased by ethanol treatment but GTE prevented the ethanol-induced glutathione decrement. The levels of liver marker enzymes (AST, ALT), liver antioxidant enzymes (SOD, CAT, GPx) and lipid peroxidation marker (TBARS) were not changed in rats of 1 and 3 hours after ethanol treatment. After 20 days, GTE decreased the changes of liver marker enzymes (AST, ALT) activities and TBARS level by ethanol. This study shows that GTE beneficially modulates TNF-$\alpha$ and glutathione levels in liver of ethanol administered rats. The GTE supplementation could be beneficial to liver by decreasing early changes of biomarkers of liver damage caused by ethanol.

Effect of the Toluene Administration on the Liver Damage in Rats Fed Low or Standard Protein Diet (저 및 표준단백식이로 성장시킨 흰쥐에 Toluene 투여가 간 손상에 미치는 영향)

  • 윤종국;김경순;임영숙
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.6
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    • pp.981-985
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    • 1996
  • To study the effect of toluene administration on the liver damage, rats were previously fed a low (casein 7%, LP) or standard(casein 20%, SP) protein diet and for four days toluene(50% in olive oil) was given at 0.2ml/100g body weight/day to the male rats, and then the degree of liver damage in toluenetreated animals fed LP were compared with those fed SP. The increasing rate of liver weight/body weight and the serum levels of xanthine oxidase to the control group were higher in rats fed SP than those fed LP. The decreasing rate of protein contents in cytosol, mitochondria and glycogen, glutathione contents of liver to the control group were higher in rats fed SP than those fed LP. In histopathological findings, the swelling of hepatic cell around the central vein was demonstrated in all the two groups toluene-treated rats. But the degree of swelling severity in hepatocytes was somewhat higher in rats fed SP than those fed LP. Therefore it is assumed that the degree of liver damage severity in toluenetreated animals was higher in rats fed SP than those fed LP.

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Processed Panax ginseng, Sun Ginseng, Decreases Oxidative Damage Induced by tert-butyl Hydroperoxide via Regulation of Antioxidant Enzyme and Anti-apoptotic Molecules in HepG2 Cells

  • Lee, Hye-Jin;Kim, Jin-Hee;Lee, Seo-Young;Park, Jeong-Hill;Hwang, Gwi-Seo
    • Journal of Ginseng Research
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    • v.36 no.3
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    • pp.248-255
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    • 2012
  • Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

Effects of Daesihotang and its component groups on diabetes, free radical and antioxidative defense system in alloxan induced diabetic rats (대시호탕(大柴胡湯)이 alloxan으로 유발(誘發)된 고혈당(高血糖) 백서(白鼠)에 미치는 영향(影響))

  • Park, Seon-Dong;Yun, Byeong-Guk
    • Herbal Formula Science
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    • v.9 no.1
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    • pp.289-317
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    • 2001
  • The purpose of this study was to reseach the effect of Daesihotang and its component groups on diabetes, free radical and antioxidative defense system in alloxan-induced diabetic rats. The experimental group was divided into three groups: Daesihotang (DS), Soyangyak (DS1), Yangmyungyak (DS2). The results were obtained as follows: The level of glucose, triglyceride, total cholesterol, creatinine in serum were considerablely reduced by Daesihotang. And the level of HDL cholesterol, albumin, total protein in serum were increased by Daesihotang significantly. And the level of BUN has some decreased, but with no significancy. In the study of Daesihotang on free radical scavenging effect in vitro, it has shown that Daesihotang and its components group have significant suppressing effect on peroxidation of linoleic acid on concentration. And in other experiments as scavenging effect of DPPH radical, inhibitory effect of superoxide in xanthine-xanthine oxidase system and inhibitory effect on lipid peroxidation reaction by hydroxy radical in $H_2O_2-Fe^{2+}$ system, Daesihatang have some activity, but with no significancy. In the study of Daesihotang on antioxidative defense system in vivo, the activity of GOT and GPT in serum were significantly increased; and the amounts of lipid peroxide in serum was reduced significantly but in liver no significancy. In hepatic catalase activity, Daesihotang has showed significant effect. In the level of hepatic glutathione, Daesihotang increased the amount of glutathione significantly. And in the activity of glutathione-s-transferase, Daesihotang has decreasing effect but has no significancy. These result suggest that Daesihotang has strong effect on diabetes and it is useful to prevent diabetes, but has less effect on peroxidative damage by free radical.

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Effect of Panax ginseng on the Development and Loss of Morphine Tolerance and Dependence (인삼이 몰핀의 내성 및 의존성 형성에 미치는 영향)

  • Kim Hack Seang;Oh Ki Wan
    • Proceedings of the Ginseng society Conference
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    • 1988.08a
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    • pp.151-155
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    • 1988
  • The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins(SP), protopanaxadiol saponins (PD), and protopanaxatriol saponins(PT) on the development of morphine-induced tolerance and physical dependence in mice. The study also sought to determine the hepatic glutathione contents. which are closely related to the degree of detoxification of mine the effects of GS on morphine 6-dehydrogenase, which catalyzes the production of morphinone from morphine, and the roles of spinal descendign inhibitory systems in the production of antagonism. The results of the present study showed that GS, PD and PT administered orally inhibited the development of morphine induced tolerance and dependence. GS. PD and PT inhibited the reduction of hepatic glutathione concentration in mice treated chronically with morphine and the activity of morphine 6-dehydrogenase, and the activation of spinal descending inhibitory systems was inhibited by GS. So we hypothesized that the results were partially due to the dual action of the test drugs, the inhibition of morphinone production and the activated formation of morphinone-glutathinone conjugation, and the inhibition of the activatin of apinal descending inhibitory systems and the others.

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