• Journal of Ginseng Research
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• v.27 no.1
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• pp.1-10
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• 2003

In present study, we examined whether or not the pretreatment of Korean Red Ginseng (KRG) could protect hepatotoxicity induced by carbon tetrachloride (CCl$_4$) and D-galatosamine (GalN). For this study, we not only tested activity of various plasma enzymes (AST, ALT, SDH, LDH), which are used as indicators of liver disease, but also checked the change of liver components such as lipid, glutathione and cytochromes content, and several liver enzyme activity. Pretreatment of KRG for two weeks significantly reduced the elevated plasma enzyme activities induced by CCl$_4$ and GalN. Pretreatment of KRG also restored the hepatic enzymes, malonedialdehyde formation, and depletion of reduced glutathione content induced by CCl$_4$ and GalN to near normal level. However, ${\gamma}$-glutamylcysteine synthetase activity was lot affected by KRG. These results suggest that KRG shows the hepatoprotective effect by reducing lipid peroxidation, by reducing the activity of free radical generating enzymes, and by preserving the hepatic glutathione.

• Toxicological Research
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• v.17
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.641-645
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• 2007

Delphinidin, an aglycone form of anthocyanins, was demonstrated to have anti-carcinogenic potential. The compound at $50\;{\mu}g/mL$ caused a significant increase of quinone reductase activity, an anti-carcinogenic marker enzyme, in mouse hepatoma cell lines (Hepa1c1c7 and BPRc1). Delphinidin enhanced the expression of other detoxifying or antioxidant enzymes including glutathione s-transferase, gamma-glutamylcysteine synthetase, heme oxygenase 1, and glutathione reductase. It suppressed the proliferation of murine hepatoma cells in a dose-dependent manner, with approximately $IC_{50}$ of $70\;{\mu}g/mL$. These results suggest that delphinidin might be useful for cancer prevention.

• The Korean Journal of Mycology
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• v.31 no.1
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• pp.34-39
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• 2003

This study was conducted to investigate effects of Ramaria botrytis methanol extract on liver damage in benzo$({\alpha})$pyrene(B$({\alpha})$P)-treated mice. The activities of serum amminotransferase, cytochrome P-450, aminopyrine N-demethylase, aniline hydroxylase and hepatic content of lipid peroxide after B$({\alpha})$P-treatment were increased than control, but those levels were significantly decreased by the treatment of Ramaria botrytis methanol extract. Whereas, the hepatic glutathione content and activities of glutathionie S-transferase and r-glutamylcysteine syntherase were increased by the treatment of Ramaria botrytis methanol extract. In addition, cytochrome P-450 1A1 izozyme protein level, remarkably increased by B$({\alpha})$P-treatment was decreased by the treatment with methanol extract of Ramaria botrytis. These results suggest that the protective effect of methanol extract of Ramaria botrytis on liver injury in B$({\alpha})$P-treated mice may be due to reduction of oxygen free radical.

• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1539-1545
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• 2010

In beer, glutathione works as the main antioxidant compound, which also correlates with the stability of the beer flavor. In addition, high residual sugars in beer contribute to major nonvolatile components, which are reflected in a high caloric content. Therefore, in this study, the Saccharomyces cerevisiae GSH1 gene encoding glutamylcysteine synthetase and the Saccharomycopsis fibuligera ALP1 gene encoding ${\alpha}$-amylase were coexpressed in industrial brewing yeast strain Y31 targeting the ${\alpha}$-acetolactate synthase (AHAS) gene (ILV2) and alcohol dehydrogenase gene (ADH2), resulting in the new recombinant strain TY3. The glutathione content in the fermentation broth of TY3 increased to 43.83 mg/l as compared with 33.34 mg/l in the fermentation broth of Y31. The recombinant strain showed a high ${\alpha}$-amylase activity and utilized more than 46% of the starch as the sole carbon source after 5 days. European Brewery Convention tube fermentation tests comparing the fermentation broths of TY3 and Y31 showed that the flavor stability index for TY3 was 1.3-fold higher, whereas its residual sugar concentration was 76.8% lower. Owing to the interruption of the ILV2 gene and ADH2 gene, the contents of diacetyl and acetaldehyde as off-flavor compounds were reduced by 56.93% and 31.25%, respectively, when compared with the contents in the Y31 fermentation broth. In addition, since no drug-resistant genes were introduced to the new recombinant strain, it should be more suitable for use in the beer industry, owing to its better flavor stability and other beneficial characteristics.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.77-83
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• 2024

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ_25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ_25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ_25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ_25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ_25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ_25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

• Microbiology and Biotechnology Letters
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• v.19 no.6
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• pp.575-582
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• 1991

To increase the production of glutathione by the expression of recombinant gsh plasmids, two genes responsible for the biosynthesis of glutathione were isolated and cloned. To clone a gshI gene, the GS903 mutant strain, which is deficient in $\gamma$-glutamylcysteine synthetase activity, has been raised. A gshI gene was cloned using pBR322 plasmid as a 3.6 Kb PstI DNA fragment isolated from E. coli K-12 chromosomal DNA. Also a gshIl gene was cloned using pUC13 plasmid as a 2.2 Kb PstI-BamHI DNA fragment. To study the effects of plasmid copy number and passenger DNA size on the expression levels of the gsh genes, various recombinant plasmids containing different sets of genes were constructed. The expression levels of the gsh genes were increased approximately twice higher in pUC series plasmids than that in pBR322 plasmid. But the sizes of the passenger DNA containing the gsh genes in the vector plasmid did not affect on the expression levels of the gsh genes.

• Journal of Life Science
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• v.14 no.1
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• pp.148-153
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• 2004

In this study, we investigated the effect of water, extract of Terminalia Chebula (TC) on physiological activity in mice. TC water extract showed hemagglutination against several different types of red blood cells. $LD_{50}$ of TC extract was 390 mg/kg (po). Treatment of TC water extract orally administered 200, 300 mg/kg daily for one week. Hepatic cytosolic enzymes, xanthine oxidase and aldehyde oxidase activities were significantly increased comparison with normal group. Treatment of TC water extract increased hepatic malondialdehyde (MDA) formation, and reduced glutathione content. We also found that the decreased activities of glutathione S-transferase and glutathione reductase but was not affected activities of $\gamma$-glutamylcysteine synthetase after treatment of TC water extract. These results suggested that increase of the hepatic lipid peroxide is caused by glutathione reduction.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.6
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• pp.702-708
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• 1993

The study was attempted to elucidate the mechanism of GE-132(100mg/kg, p.o. for 6 weeks) on the metabolism of bromobenzene (460mg/kg, i.p. bid, for 2 days), which has potent carcinogenicity, mutagenicity and hepatotoxicity. It showed that activities of cytochrome p-450, aminopyrine demethylase and aniline hydroxylase, which have epoxide generating property, were not changed by GE-132 treatment. On the other hand, epoxide hydrolase was not changed but that glutathione S-transferase was significantly increased by GE-132 treatment. And also ${\gamma}-glutamylcysteine$ synthetase was not changed following the GE-132 treatment, but the activity of glutathione reductase was significantly increased. The level of hepatic glutathione which was decreased by bromobenzene recovered markedly by GE-132 pretreatment. It is concluded that the mechanism for the observed effect of GE-132 on bromobenzene metabolism is due to the induction of glutathione S-transferase.

• 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.