• 제목/요약/키워드: Glutathione Level

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Effects of the Methanol Extract of the Leaves of Brassica juncea and Its Major Component, Isorhamnetin $3-O-{\beta}-D-Glucoside$, on Hepatic Drug Metabolizing Enzymes in Bromobenzene-treated Rats

  • Hur, Jong-Moon;Choi, Jong-Won;Park, Jong-Cheol
    • Food Science and Biotechnology
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    • 제16권3호
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    • pp.439-443
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    • 2007
  • The effects of the methanol extract of the leaves of Brassica juncea and isorhamnetin $3-O-{\beta}-D-glucopyranoside$, major compound isolated from the ethyl acetate fraction of this plant on hepatic lipid peroxidation and drug-metabolizing enzymes, were evaluated in rats treated with bromobenzene. The extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ of oral administration did not show any significant effects on activities of aminopyrine N-demethylase and aniline hydroxylase, enzymes forming toxic epoxide by bromobenzene as well as on glutathione content. However, both methanol extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ significantly recovered the decreased activities of glutathione s-transferase and epoxide hydrolase, and also reduced the lipid peroxide level in rats treated with bromobenzene. From the results, the protections of this plant against bromobenzene-induced hepatotoxicity are thought to be via enhancing the activities of epoxide hydrolase and glutathione s-transferase, enzymes removing toxic epoxide, and reducing the lipid peroxide level.

Changes in drug metabolism during hypoxia/reoxygenation in isolated perfused rat

  • Seo, Min-Young;Cho, Tai-Soon;Lee, Sun-Mee
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1997년도 춘계학술대회
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    • pp.98-98
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    • 1997
  • This study was done to investigate the effect of vitamin E on hypoxia/reoxygenation-induced hepatic injury in isolated perfused rat liver. Rats were pretreated with vitamin E or vehicle(soybean oil). Isolated livers from fasted 18 hours were subjected to 45min of low flow hypoxia or N$_2$ hypoxia followed by reoxygenation for 30min. The perfusion medium used was KHBB(pH 7.4) and 50${\mu}$㏖/$\ell$ of ethoxycoumarin was added to the perfusate to determine the ability of hepatic drug-metabolizing systems, In low flow hypoxia model, total glutathione and oxidised glutathione levels were significantly increased by hepoxia/reoxygenation with slight increase in LDH levels. These increases were prevented by vitamin E pretreatment. In N$_2$ hypoxia model, LDH, total glutathione and oxidized glutathione levels were increased significantly by hypoxia but restored to normal level by reoxygenation. Vitamin E had little effect on this hypoxic damage. There were no significant changes in the rate of hepatic oxidation of 7-EC to 7-HC in both hepoxic models. But, the subsequent conjugation of 7-HC by sulfate or glucuronic acid were significantly decreased by hypoxia, but restored by reoxygenation in both hypoxia models. As opposed to our expectation, treatment with vitamin E aggrevated the decrease of the rate of conjugation and even inhibited the restoration by reoxygenation. Our findings suggest that hypoxia/reoxygenation diminishes phase II drug metabolizing function and this is, in part, related to decreased energy level.

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흰쥐의 분리 간세포에서 스트렙토조토신의 독성 (Toxicity of Streptozotocin in Isolated Rat Hepatocytes)

  • 박기숙;정정철;문창규;정진호
    • 약학회지
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    • 제36권1호
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    • pp.80-86
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    • 1992
  • Streptozotocin (STZ) is a naturally occurring nitrosoamide used extensively to produce diabetes in experimental animals. Our previous study has demonstrated that i.v. administraton of streptozotocin induces significant red blood cell hemolmysis in rats. Since it has been reported that the highest concentration of STZ is found in the liver, the effect of STZ in freshly isolated rat hepatocytes has been investigated. STZ treatment (10 mM) did not cause significant loss of viability throughout 4 hour incubation, while high dose of STZ (300 mM) to hepatocytes resulted in complete cell death within 3 hours. Addition of 40 mM glucose to incubation medium did not potentiate STZ-induced hepatotoxicity, suggesting that STZ-induced hyperglycemia in vivo did not affect its hepatotoxicity. To investigate the mechanixm of the toxicity, intracellular total glutathione level was determined. Tratment with 10 mM STZ which was not toxic to hepatocytes led to complete depletion of intracellular glutathione level within 1 hour incubation. These results suggest that STZ-induced hepatotoxicity may be independent on the intracellular glutathione depletion.

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Esculetin Inhibits Adipogenesis and Increases Antioxidant Activity during Adipocyte Differentiation in 3T3-L1 Cells

  • Kim, Younghwa;Lee, Junsoo
    • Preventive Nutrition and Food Science
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    • 제22권2호
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    • pp.118-123
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    • 2017
  • This study was conducted to investigate the anti-adipogenic activity of esculetin (ECT) which is reported to be attributable to the modulation of antioxidant enzymes during adipogenesis. After six days of ECT treatment of 3T3-L1 cells, lipid accumulation was determined by Oil red O staining. The levels of glutathione (GSH) and reactive oxygen species (ROS), and the activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase (GPx), and catalase were examined. In addition, the protein expression of glutamate-cysteine ligase catalytic subunit (GCLC) and heme oxygenase-1 (HO-1) was measured by Western blot. ECT significantly inhibited lipid accumulation by approximately 80% and ROS production in a concentration-dependent manner. GSH level and GPx activity were increased by ECT by approximately 1.3-fold and 1.7-fold compared to the control group, respectively. GCLC and HO-1 expression were elevated by ECT. These results showed that ECT treatments strongly inhibit adipogenesis, increase GSH level, and upregulate the expression of GCLC and HO-1, possibly by decreasing ROS production in 3T3-L1 cells during adipogenesis.

Roles of Glutathione Reductase and $\gamma$-Glutamylcysteine Synthetase in Candida albicans

  • Baek, Yong-Un;Yim, Hyung-Soon;Kang, Sa-Ouk
    • 한국생물물리학회:학술대회논문집
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    • 한국생물물리학회 2003년도 정기총회 및 학술발표회
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    • pp.61-61
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    • 2003
  • We have cloned the CGR1 gene encoding glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH) from Candida albicans. The cgr1/cgr1 mutants were not viable when CaMAL2 promoter repressed the CGR1 expression. The growth of the mutants could be partially overcome by thiol compounds such as GSH, dithiothreitol, cysteine, N-acetylcysteine and GSSG. Interestingly, C. albicans with CGR1 overexpressed showed defective hyphal growth on solid medium and attenuated virulence. We have also cloned the GCS1 gene encoding ${\gamma}$-glutamylcysteine synthetase which catalyzes the first step of glutathione biosynthesis. The gcs1/gcs1 mutants were nonviable in minimal defined medium. The growth of the mutants could be resumed by supplementing with GSH, GSSG and ${\gamma}$-glutamylcysteine in the medium. The mutants had increased intracellular D-erythroascorbic acid level up to 2.25-fold when transferred to GSH-free medium. When the mutants were depleted of GSH, they showed typical markers of apoptosis. In conclusion, these results suggest that glutathione is an essential metabolite, and involved in hyphal growth, virulence and apoptosis in C. albicans.

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식이성 Tungstate가 사염화탄소 투여에 의한 흰쥐 간 손상에 미치는 영향 (Effect of Dietary Tungstate on the Liver Damage in $CCl_4$-treated Rats)

  • 윤종국;박해숙;이상일
    • 한국식품영양과학회지
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    • 제22권6호
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    • pp.678-684
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    • 1993
  • To evaluate the role of xanthine oxidase in liver damage by CCl4, a group of rats were fed tungstate for a month, which suppressed the activities of xanthine oxidase in serum and liver. Control group of rats were fed standard diet without tungstate. Liver damage was induced both in tungstate fed and control groups by two intraperitoneal injections of CCl4 at the level of 0.1ml/100g body weight at intervals of 24 hours. Increases in the levels of serum alanine aminotransferase by CCl4 were significantly smaller in tungstate fed rats than in control rats. Concomitantly, histopathologic changes were less in tungstate fed rats than in control ones. In rats either treated with CCl4 or not, hepatic type O xanthine oxidase activities were remarkably reduced by tungstate feeding. Hepatic aniline hydroxylase activities were higher in rats fed tungstate than control rats when animals were not treated with CCl4, but the enzyme activities were lower in tungstate fed rats than control when they were treated with CCl4. Neither tungstate feeding nor CCl4 treatment caused any significant changes in hepatic glutathione contents, and activities of hepatic glutathione S-transferase, glutathione peroxidase and superoxide dismutase. It is concluded xanthine oxidase reaction augment CCl4 induced liver damage via oxygen free radical system.

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고혈당 흰쥐에서 상엽(桑葉)의 혈당 조절과 항산화 작용에 관한 연구 (Effects of the Mori folium Extract in Streptozotocin-Induced Diabetic Rats)

  • 김오곤;정지천
    • 대한한방내과학회지
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    • 제27권4호
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    • pp.811-821
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    • 2006
  • Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many methods have been tried to regulate oxygen free radicals for treating diabetes and its complications. Because Mori foliumhas been known to be effective for the treatment of diabetes, the methanol extract of Mori folium was tested for its effectiveness in reducing the oxidative stress induced by streptozotocin. Methods : The crushed Mori folium was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ or 24 h. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 11.7 g. Mori folium extract was oral-administered to diabetic rats induced by streptozotocin at 100 mg per 1 kg of body weight for 20 days. The efficacy of the Mori foliumextract was examined with regard to the enzymatic pathways involved in oxygen free radical production and glutathione balance. Results : The effects of the Mori foliumin streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin level, hepatic lipid peroxide level, hepatic glutathione level, hepatic glutathione S-transferase and glutathione peroxidase level, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were shown to be good enough to cure and prevent diabetes and its complications. Conclusions : These results indicated that Mori folium might reduce oxidative stress in tissues and organs by regulating the production of oxygen free radicals. Especially Mori folium might prevent and cure diabetes and its complications by reducing oxidative stress in the ${\beta}-cells$ of the pancreas.

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Protective Effect of Diallyl Disulfide on Ethacrynic Acid-Inducted Toxicity in Mice

  • Huh, Keun;Lee, Sang-Il;Song, Jae-Woong
    • Archives of Pharmacal Research
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    • 제10권3호
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    • pp.149-152
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    • 1987
  • The present work was undertaken to investigate the effect of diallyl disulfide on ethacrynic acid toxicity. Ethacrynic acid-induced morality and formation of lipid peroxide were inhibited by diallyl disulfide. Furthermore, decreasing effect of glutathione S-transferase and glutathione level in the liver by ethacrynic acid were reduced by diallyl disulfide. These results suggested that the inducing effect of diallyl disulfide on the ethacrynic acid metabolizing enzyme, glutathione S-transferase, is believed to be a possible detoxication mechanism for the ethacrynic acid toxicity in mice.

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Protective Effect of Sachungwhan against CCl4-induced Hepatotoxicity

  • Koo, Ja-Young;Jung, Ki-Hwa
    • Biomolecules & Therapeutics
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    • 제14권4호
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    • pp.207-215
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    • 2006
  • Sachungwhan reduced hepatotoxicity induced by carbon tetrachloride($CCl_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine(CRE), total cholesterol(TCHO), triglyceride(TG), low density lipoprotein cholesterol(LDL-CHO), high density lipoprotein cholesterol(HDL-CHO), total protein(TP), albumin(ALB) and total bilirubin(BIL) in serum. Hepatic parameters monitored were levels of cholesterol(CHO), triglyceride(TG), malondialdehyde(MDA), content of cytochrome P450(CYP), level of glutathione(GSH), and activities of NADPH-CYP reductase, superoxide dismutase(SOD), catalase(CAT), glutathione S-transferase(GST), glutathione reductase(GR), glutathione peroxidase(GPx). The histopathological examination showed that the treatment of Sachungwhan relieved the ballooning degeneration of hepatocytes which had been generated by $CCl_4$. The results suggested that hepatoprotective effects of Sachungwhan possibly are due to their promising antioxidative activity.

Effects of grape pomace on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

  • Choi, Chang-Sook;Chung, Hae-Kyung;Choi, Mi-Kyung;Kang, Myung-Hwa
    • Nutrition Research and Practice
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    • 제4권2호
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    • pp.114-120
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    • 2010
  • The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing $H_2O_2$ that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia.