• Title/Summary/Keyword: Glutathione reductase

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Protective Effects of Acetylbergenin against Carbon Tetrachloride Induced Hepatotoxicity in Rats

  • Lim, Hwa-Kyung;Kim, Hack-Seung;Kim, Seung-Hwan;Chang, Myung-Jei;Rhee, Gyu-Seek;Choi, Jong-Won
    • Archives of Pharmacal Research
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    • v.24 no.2
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    • pp.114-118
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    • 2001
  • The present study was undertaken to investigate whether or not the hepatoprotective activity of acetylbergenin was superior to bergenin in carbon tetrachloride ($CCl_4$)-intoxicated rat. Acetylbergenin was synthesized by acetylating bergenin, which was isolated from Mallotus japonicus. The hepatoprotective effects of acetylbergenin were examined against $CCl_4$-induced liver damage in rats by means of serum and liver biochemical Indices. Acetylbergenin was administered orally once daily for 7 successive days, then a 0.5 ${m/kg}$ mixture of $CCl_4$in olive oil (1:1) was intraperitoneally injected at 12 h and 36 h after the final administration of acetylbergenin. Pretreatment with acetylbergenin reduced the elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and $\gamma$-glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content dose dependently in $CCl_4$-intoxicates rats. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored to almost normal levels. The results of this study strongly suggest that acetylbergenin n has potent hepatoprotective activity against $CCl_4$-induced hepatic damage in rats by glutathione-mediated detoxification as well as having free radical scavenging activity. In addition, acetylbergenin doses of 50 ${mg/kg}$showed almost the same levels of hepatoprotection activity as 100 ${mg/kg}$ of bergenin, indicating that lipophilic acetylbergenin is more active against the antihepatotoxic effects of $CCl_4$ than those of the much less lipophilic bergenin.

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Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats

  • Lu, Kuan-Hung;Weng, Ching-Yi;Chen, Wei-Cheng;Sheen, Lee-Yan
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.316-325
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    • 2017
  • Background: Ginseng essence (GE) is a formulation comprising four medicinal and edible herbs including ginseng (Panax ginseng), American ginseng (Panax quinquefolius), lotus seed (Nelumbo nucifera), and lily bulb (Lilium longiflorum). This study was aimed at investigating the hepatoprotective effect of GE against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Methods: We treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight (bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After the 1st wk of treatment, rats were administered 20% $CCl_4$ (1.5 mL/kg bw) two times a week to induce liver damage until the treatment ended. Results: Serum biochemical analysis indicated that GE ameliorated the elevation of aspartate aminotransferase and alanine aminotransferase and albumin decline in $CCl_4$-treated rats. Moreover, $CCl_4$-induced accumulation of hepatic total cholesterol and triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing the hepatic antioxidant defense system including glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase. In addition, histological analysis using hematoxylin and eosin and Masson's trichrome staining showed that GE inhibited $CCl_4$-induced hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of alpha-smooth muscle actin indicated that $CCl_4$-triggered activation of hepatic stellate cells was reduced. Conclusion: These findings demonstrate that GE improves $CCl_4$-induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

Antioxidant Action of Ginseng : An hypothesis (인삼의 항산화 작용)

  • Lee, D.W.;Sohn, H.O.;Lim, H.B.;Lee, Y.G.;Aprikian, A.G.;Aprikian, G.V.
    • Journal of Ginseng Research
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    • v.19 no.1
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    • pp.31-38
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    • 1995
  • Antioxidant effect of Korean ginseng (Panax ginseng C.A. Meyer) was investigated in rats. Long-term administration of ginseng water extract protected the activity of liver cytosotic SOD, catalase and glutathione peroxidase from being significantly decreased with advancing age (p<0.05). It was more effective toward glutathione peroxidase than other antioxidant enzymes. However, the level of sulfhydryl compounds and its related enzymes such as glutathione reductase and glutathione-5-transferase was not significantly changed by the administration of ginseng. Liver microsomal formation of reactive oxygen species such as superoxide and hydrogen peroxide did not show a significant difference between two groups although it was slightly decreased with age, but lipid peroxidizability of microsomal membrane induced by a prooxidant was slightly lower in ginseng-treated rats. Interestingly, antioxidant capacity of plasma from ginseng treated rats on autooxidation of ok-brain homogenates was much higher than that of normal ones. However, resistance of RBC membrane against oxidative stress showed a similar tendency. The content of serum TBA reactive substances lowered consistently in the rats treated with r ginseng at all corresponding age and a significant difference between two groups was found at 24 months of age (p<0.05). Ginseng extract protected lipid peroxidation in brain and liver. This protection was more effective in the stressed rats imposed by immobilization than normal ones. In conclusion, ginseng water extract protected the age related deterioration of major antioxidant enzymes, and this effect was more striking with increasing duration of treatment. This comprehensive antioxidant action of ginseng seems to be bra certain action of ginseng other than a direct antioxidant action, which might be a long term normalizing effect through the harmony of various components.

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The Mechanism of Nephrotoxicity Formation of Methotrexate in STZ-Induced Hyperglycemic Rats (Streptozotocin 유도 당뇨성 흰쥐에서 methotrexate의 신독성 생성기전에 관한 연구)

  • Kim Seok-Hwan;Kim Yeo-Jeong;Lee Joo-Yeon;Kang Hye-Ok;Lee Hang-Woo;Choi Jong-Won
    • Journal of Life Science
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    • v.16 no.2 s.75
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    • pp.259-265
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    • 2006
  • This study is investigated the effect on mechanism of nephrotoxicity formation of methotrexate(MTX) by hyperglycemic by streptozotocin(STZ). MTX was injected daily at two doses of 3, 6 mg/kg for 1 week in STZ-induced hyperglycemic rats. Activities of BUN, creatinine and LDH were significantly increased by treatment with MTX in STZ-induced diabetic group when compared to MTX treatment group in normal rats' Renal lipid peroxide content and activities of cytosolic enzyme were significantly increased in the treatment of MTX in diabetic group. The concentration of glutathione and glutathione biosynthesis enzymes were decreased by treatment with MTX in STZ-induced diabetic group. These results suggest that nephrotoxicity of MTX in STZ-induced hyperglycemic rat was caused by activation of renal metabolizing enzymes in cytosol and decrease of glutathione concentration.

The Effect of Korean Red Ginseng Water-extract on Aging-related Changes in the Xenobiotic Metabolizing Enzyme System in the Liver of Rats (홍삼의 물추출물이 노화에 따른 흰쥐 간의 이물질대사 효소계에 미치는 영향)

  • Lee, Dong-Wook;Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.6
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    • pp.329-335
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    • 2006
  • The present study was designed to investigate aging-related effects on the activities of xenobiotic metabolizing enzymes of rat liver by dietary supplementation of Korean red ginseng water-extract. Rat did not show any discernible signs of the rejection symptoms, and blood GOT and GPT levels were not influenced by ginseng water extracts, Cytochrome 450 levels and NADPH cytochrome P45O reductase, p-450 dependent ethoxycoumarin O-deethylase, and benzphetamine N-demethylase activities were decreased with aging, however, these phase I system enzymes activities in the ginseng group of24 months were well maintained compared with normal group. But, Levels of cytochrome bs and NADH-cytochrome b$_5$ reductase activities were also decreased with aging and were not found a clear difference between two groups. Glutathione-s-transferase activity, phase II enzyme system, in liver cytosols was also decreased in old ages, but the degree of decrease was higher in normal group than in giuseng supplemented group. These results indicate that long-term supplementation of red ginseng water extracts from weaning to 24 months do not show any side effects to rats, and retard age-related deteriorations of xenobiotic metabolizing enzymes activities in old ages.

Scavenging Reactive Oxygen Species by Rice Dehydroascorbate Reductase Alleviates Oxidative Stresses in Escherichia coli

  • Shin, Sun-Young;Kim, Il-Sup;Kim, Yul-Ho;Park, Hyang-Mi;Lee, Jang-Yong;Kang, Hong-Gyu;Yoon, Ho-Sung
    • Molecules and Cells
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    • v.26 no.6
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    • pp.616-620
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    • 2008
  • Maintaining redox balance is one of the crucial requirements for a cell to endure stress from the outside. Dehydroascorbate reductase (DHAR; EC 1.8.5.1) plays an important role in the ascorbate-glutathione cycle; one of the major ROS scavenging systems in most known biological systems. A cDNA clone of the DHAR gene from Oryza sativa (OsDHAR) was isolated and overexpressed in Escherichia coli BL21 (DE3) strain from the pET-28a(+) expression vector. The OsDHAR transformed E. coli cells showed significantly higher DHAR activity and a lower level of ROS than the E. coli cells transformed by an empty pET-28a(+) vector. Also, the DHAR-overexpressing E. coli strain was more tolerant to oxidant- and heavy metal-mediated stress conditions than the control E. coli strain. The results suggest that the overexpressed rice DHAR gene effectively functions in a prokaryotic system and provide protection to various oxidative stresses.

Sulforaphane is Superior to Glucoraphanin in Modulating Carcinogen-Metabolising Enzymes in Hep G2 Cells

  • Abdull Razis, Ahmad Faizal;Noor, Noramaliza Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4235-4238
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    • 2013
  • Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 ${\mu}M$) for 24 hours. Glucoraphanin at higher concentration (25 ${\mu}M$) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 ${\mu}M$. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen-metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.

Suppressive Effects of Young Radish Cultivated with Sulfur on Growth and Metastasis of B16-F10 Melanoma Cells

  • Kim Soo-Jin;Kim Byung-Sam;Kyung Tae-Wook;Lee Sang-Chul;Rho Chi-Woong;Choi Kyung-Rak;Hwang Hae-Jun;Choi Hye-Seon
    • Archives of Pharmacal Research
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    • v.29 no.3
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    • pp.235-240
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    • 2006
  • The oral administration of extracts of young radishes cultivated with sulfur after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in mice. Treatment of the mice with extracts of young radish cultivated with sulfur did not show any increase in the number of CD8+ or NK T cells in the spleen, indicating no influence on host immunity. Sulforaphane, which could be a candidate for an active compound from young radishes cultivated with sulfur, inhibited cell growth of B16-F10 melanoma cells. In addition, extracts of the young radish cultivated with sulfur-fed group showed enhanced quinine reductase (QR) activities in the liver and lung and a slight increase of glutathione S-transferase (GST) activity in the liver. These results suggested that the administration of extracts of young radishes cultivated with sulfur suppressed pulmonary tumorigenesis, possibly due to increased activity of detoxification enzymes in the liver and lung, and partly due to cell cytotoxicity.

(-) Epigallocatechin gallate restores ethanol-induced alterations in hepatic detoxification system and prevents apoptosis

  • Anuradha, Carani V;Kaviarasan, Subramanian
    • Advances in Traditional Medicine
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    • v.7 no.3
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    • pp.311-320
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    • 2007
  • The present study was designed to estimate the protective effect of (-) epigallocatechin gallate (EGCG) on ethanol-induced liver injury in rats. Chronic ethanol administration (6 g/kg/day ${\times}$ 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction - aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin and ${\gamma}$-glutamyl transferase in plasma and reduction in liver glycogen. The activities of alcohol metabolizing enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase were found to be altered in alcohol-treated group. Ethanol administration resulted in the induction of cytochrome p450 and cytochrome-$b_{5}$ activities and reduction of cytochrome-c reductase and glutathione-S-transferase, a phase II drug metabolizing enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by trypan blue exclusion test and induced hepatocyte apoptosis as assessed by propidium iodide staining. Treatment of alcoholic rats with EGCG restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and drug metabolizing enzymes and cyt-c-reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in alcohol + EGCG-treated rats. These findings suggest that EGCG acts as a hepatoprotective agent against alcoholic liver injury.

Effects of Dietary Mushroom on Blood Glucose Levels, Lipid Concentrations and Glutathione Enzymes in Streptozotocin-Induced Diabetic Rats (식이 중 표고버섯의 섭취가 당뇨유발쥐의 혈당과 지질농도 및 Glutathione효소계에 미치는 영향)

  • 조영자;김현아;방미애;김은희
    • Journal of Nutrition and Health
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    • v.35 no.2
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    • pp.183-191
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    • 2002
  • The purpose of this study was to investigate the effect of dietary mushroom powder on blood glucose levels, seam lipid levels, glucose 6-phosphtase (G6Pase), thiobarbituric arid reactive substance (TBARS) and glutathione enzymes in diabetic rats treated with streptozotocin (STZ). Four groups of rats (Sprague-Dawley male rats, 180-200 g) were fed as follows: normal rats were fed a control diet (C), diabetic rats were file a control diet (CD), normal fats were fed a mushroom powder diet (M), and diabetic rals were find mushroom powder diet (MD). Diabetes was induced by single injection of streptozotocin (60 mg/kg B.W.). The animals were fed ad libium each of the experimental diets for five weeks. Food and water intake was determined every day. Blood glucose and serum total cholesterol levels were determined every week. After five weeks, the rats were sacrificed and blood glucose, serum total cholesterol, triglyceride levels and glutathione enzymes were measured. HDL-cholesterol levels were analyzed and LDL-cholesterol concentrations were calculated by equation. There was body weight loss in the diabetic rats, but the MD group showed less body weight loss than the CD group. Blood glucose and serum total cholesterol level of the MD group were lower than those of the CD group (p < 0.05). Also, serum total cholesterol of the M group was lower than that of the C group (p < 0.05). But the serum triglyceride level of the diabetic rats (CD and MD) was higher than that of the normal rats (C and M). However, there was no significant difference between the control diet group and the mushroom diet group. Serum HDL-cholesterol levels of the C group and CD group were higher than that of the M group (p < 0.05), and the MD group was not significantly different. But the serum LDL-cholesterol levels of the M group were lower than those of the C group (p < 0.05). Activity of hepatic microsomal G6Pase significantly increased in the CD and MD, reaching levels higher than those of the C and M groups. Hepateic gutathione S-transferase (GST, glutathione reductase (GR) and glutathione peroxidase (GPX) activity was not significant. But renal GST, GR and GPX activity in the MD group was lower than that of the CD group (p < 0.05). These results suggest that dietary mushroom reduces renal disorders such as oxidation and aging of tissue. In conclusion, dietary mushroom groups reduced blood glucose and cholesterol levels in STZ-induced diabetic rats and renal glutathione enzymes activity was averted in diabetic rats.