• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.71-76
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• 1993

It has been reported that d-limonene inhibits chemical-induced rat mammary cancer by the mechanism of increases in detoxification enzymes such as glutathione S-transferases and that cineole fails to exhibit significant suppressive effect on chemical-induced carcinogenesis. The present study was designed to compare the effects of d-limonene and cineole on the benzo(a)pyrene (BP)-induced mutagenicity, BP metabolism and lipid peroxidation. Modified Ames assay was employed to evaluate the inhibitory effect of d-limonene and cineole on the BP-induced mutagenicity. The number of revertant-bearing wells was decreased by 44~77% in the presence of both BP and d-limonene compared with that of BP alone whereas cineole decreased the number of revertant-bearing wells by 28~45% at the concentrations between $2{\mu}m$m.TEX> and 2 mM. d-Limonene suppressed BP metabolism by 16, 54 and 67% at 1, 10 and 100 mM, respectively while cineole inhibited the metabolism by 16, 26 and 55% at the same concentrations. The $EC_{50}$ values for d-limonene and cineole in inhibiting lipid peroxidation were 2.0 mM and 16 mM respectively, as assayed by thiobarbituric acid method. The present study showed that d-limonene and cineole have common antimutagenic effects although d-limonone appeared to be more effective than cineole in suppressing mutation and lipid peroxidation. The results suggest that the antimutagenic effects of d-limonene and cineole may be associated with alternation in enzyme activities and with inhibition of lipid peroxidation.

• 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.

• Journal of Microbiology and Biotechnology
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• v.22 no.4
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• pp.547-554
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• 2012

Chromium is generated from several industrial processes. It occurs in different oxidation states, but Cr(III) and Cr(VI) are the most common ones. Cr(VI) is a toxic, soluble environmental contaminant. Some bacteria are able to reduce hexavalent chromium to the insoluble and less toxic Cr(III), and thus chromate bioremediation is of considerable interest. An indigenous chromium-reducing bacterial strain, Rb-2, isolated from a tannery water sample, was identified as Ochrobactrum intermedium, on the basis of 16S rRNA gene sequencing. The influence of factors like temperature of incubation, initial concentration of Cr, mobility of bacteria, and different carbon sources were studied to test the ability of the bacterium to reduce Cr(VI) under variable environmental conditions. The ability of the bacterial strain to reduce hexavalent chromium in artificial and industrial sewage water was evaluated. It was observed that the mechanism of resistance to metal was not due to the change in the permeability barrier of the cell membrane, and the enzyme activity was found to be inductive. Intracellular reduction of Cr(VI) was proven by reductase assay using cell-free extract. Scanning electron microscopy revealed chromium precipitates on bacterial cell surfaces, and transmission electron microscopy showed the outer as well as inner distribution of Cr(VI). This bacterial strain can be useful for Cr(VI) detoxification under a wide range of environmental conditions.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.178-178
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• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this Is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to ＋64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. Here, we developed luciferase reporter gene assay system to detect SXR-based CYP 3A4 transcriptional activity. We have used CYP3A4-Luc plasmid that contains proximal promoter of human CYP3A4 gene upstream of the luciferase gene. We did transient transfection of 3A4-luciferase gene and SXR. In the HepG2 cells transfected with CYP3A4-Luc, when rifampicin treatment was combined with histone deacetylase inhibitor (HDAC Inhibitor), such as Trichostatin A, Hc-toxin and IN 2001 of the luciferase activity was induced 10-20 fold over control.

• Korean Journal of Pharmacognosy
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• v.28 no.2
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• pp.88-92
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• 1997

The full NMR assignment of hispidulin 7-0-neohesperidoside (1) isolated from Cirsium japonicum var. ussuriense was made with the aid of 2D correlation NMR techniques such as HMQC and HMBC. To investigate detoxification of bromobenzene-induced hepatic lipid peroxidation by compound 1, hepatic lipid peroxide level and the activities of enzymes responsible for production and removal of epoxide were studied. The level of lipid peroxide elevated by bromobenzene was significantly reduced by compound 1. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase, glutathione S-transferase. Epoxide hydrolase activity was decreased significantly by bromobenzene, which was restored to the control level by pretreatment of persicarin. The results suggest that the bromobenzene-induced hepatic lipid peroxidation by compound 1 is reduced by enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide.

• The Korean Journal of Physiology
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• v.19 no.2
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• pp.155-160
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• 1985

Dantrolene sodium(DS) is a long acting skeletal muscle relaxant which has been successfully used to control muscle spasticity in patients with various neurological disorders. However, its use is associated with hepatotoxicity. Tissue sulfhydryl group has many important roles for cellular integration and glutathione serves as a substrate for the detoxification metabolism. The purpose of this study were to investigate the effect of DS on tissue sulfhydrl group and glutathione content. Foully albino rats were divided into two groups ; saline treated (control) and DS treated groups. DS dissolved in saline was administered orally. All rats were sacrificed after 7. 14. 21 and 28 days of DS ana saline treatment by dacapitation ana liver was removed for the enzyme preparation. Total and nonprotein sulfhydryl were measured by the method of Sedlak and Lindsay (1968). Total glutathione content was assayed according to the method described by Tietze (1969) and glutathione reductase was assayed according to the method of Racker (1955), The results obtained are summarized as follows : DS administration significantly depressed the total, protein and nonprotein sulfhydryl content in liver. There were significant reduction of both total glutathione content and glutathione reductase activity in liver. On the basis of the above results it may be speculated that the toxicity of DS are well correlated with tissue sulfhydryl content and glutathione reductase activity.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.519-528
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• 2019

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by $H_2O_2$ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.

• Molecules and Cells
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• v.45 no.12
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• pp.869-876
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• 2022

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

• Korean Journal of Medicinal Crop Science
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• v.8 no.3
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• pp.225-233
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• 2000

There was not noticeable differences in decreasing blood alcohol concentrations between Korea and China-produced Hovenia dulcis $T_{HUNB}$, showing only 1-2 % higher decreasing rate for Korea-produced seed extracts than those from China. It was also found that the blood alcohol decreasing ability was greatly enhanced by partitioning the crude extracts produced from both places. The both extracts (crude and partitioned) accelerated the reducing rate of blood alcohol concentrations down to 1-2 hours, compared to that of control (taking only ethanol). The crude extracts from imported seeds seemed to have slightly better effect on improving in vivo ADH and ALDH activities than domestic ones; however, not for partitioned extracts. It was interesting that the partitioned extracts from both countries enhanced ADH enzyme activity up to 60% than the crude, compared to the control, while ALDH activity was not much affected by the partitioned extracts. It was also confirmed that both ADH and ALDH activities were well balanced in controlling blood alcohol concentration maintaining 28-29% of enzyme activities in vivo. The extracts proved to have better effect on enhancing ALDH activity than ADH activity, which is one of possible explanation that Hovenia dulcis $T_{HUNB}$ can effectively relieve the hangover by fast decreasing acetaldehyde concentration in the liver and blood. GST activity was also increased in the range of 120 to 300% by adding crude or partitioned extracts from both countries; however, there was no difference in enhancing GST activity between the extracts from two countries. The extracts showed competitive inhibition with GST activity, showing the reduction of enzyme activity at higher than 0. 6 (g/L) of the imported extracts.

• Journal of Life Science
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• v.11 no.5
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• pp.405-414
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• 2001

Protaetia brevitarsis has been utilized as an ingredient of the description for the treatment of patients with chronic hepatic diseases in oriental medicine. This study was attempted to investigate whether Protaetia brevitarsis extract(PBE) protects or modulates the liver injuries induced by carbon tetrachloride or ethanol in Sprageue-Dawley rate. The liver injuries of rats induced by the treatment of carbon tetrachloride or ethanol were manifested by the observation of the significant changes in liver weight, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, serum thiobarbituric acid reactive substances (TBARS), and microsomal detocification enzymes(cytochrome P_450), cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase).The effect of PBF on the liver damage induced by the chemicals was evaluated with the extent modulated in change of biochemical parameters above. Exposure to ethanol alone resulted a significant change in the ration of liver per body weight, ALT activity, and microsomal detoxification enzymes (cytochrome P_450, cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase), but did not significantly changes in the levels of serum AST activity and TBARS. Pretreatment coith PBE did not modulate the alteration of the ratio of liver to body weigth, and the activities of serum aminotransferascs (AST. ALT), TBARS, and micro somal detoxification enzyme (cytochrome p_450, cytochrome b$_{5}$,and cytochrome b$_{5}$ reductase. These result suggested that PBE has not appreciable therapeutic effect on carbon tetrachloride or ethanol induced hepatotoxicity.