• Environmental Mutagens and Carcinogens
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• v.17 no.2
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• pp.97-108
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• 1997

The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

• Journal of Nutrition and Health
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• v.31 no.8
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• pp.1254-1262
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• 1998

This study has done to investigate the relationship between the icreased lipid oncentration caused by smoking and plama levels of vitamin A and vitamin E, antiodative enzyme activity, and lipid peroxidation , in 52 male smokers and 32 non-smokers, Dietary vitamin A and vitamin E intake was imilar in both smokers and non-smokers. Absolute plasma concentrations of vitamin A and vitamin E were not significantly different between two groups, whereas vitamin E/cholesterol ration in plasma was low or in smokers than in that of non-smokers(p<0.05). It was considered that this lowered effect was due to the elevated plasma lipid concentration rather than oxidant stress derived from smoking, in view of the fact that smokers had higher cholesterol (15.2%) adn LDL-C(26.6%) levels than non-smokers. In non-smokers, plasma thiobarbiturin acid reactive substances(TBARS) conrrelated positively with total cholesterol(r=0.63466, p<0.001), LDL-C level(r=0.57166, p<0.01) , and LDL-C/HDL-C ratio(r=0.45926, p<0.05) . Activities of glutathione perosidase(GSH-Px) , superoside dismutase(SOD), and catalse made no difference in both groups. However, it was observed in non-smokers that GSH-Px activity had negative correlations with total cholesterol(r=-0.67293, p<0.001), LDL-C level(r=-0.62878, p<0.001), and LDL-C/HDL-C ratio (r=-0.58824, p<0.01), indicating that there was a dependent relationship between lipid perosidation and plasma lipid level. The smokers also showed negative correlations for GSH-Px activity with total cholesterol (r=-0.29946, p<0.05) and LDL-c level (r=0.45914, p<0.001), and LDL-C/HDL-c ratio(r=-0.35438, p<0.05). It seemed that the lipid that the lipid level elevated by sustaines smoking resulted in reducing vitamin E/cholesterol ratio and proportion of antioxidant to oxidant load, and then GSH-Px activity, with insufficient removal of free radicals(TBARS 2.43$\pm$0.51 and 1.81$\pm$0.15nmol/ml in smokers and non-smokers, respectively). These findings suggest that higher plasma lipid levels may play a more important role in perturbing the antioxidant defense system including vitamin E status and GSH-Px activity, at least in circumstances that increase lipid concentration . In addition, in exposure to free radicals like those in cigarette smoke. In those cases the ratio of vitamin E/lipid in plasma can be a more indicator of vitamin E status than plasma levels of vitamin E alone.

• Journal of Life Science
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• v.18 no.3
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• pp.381-386
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• 2008

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

• Advances in Traditional Medicine
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• v.4 no.1
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• pp.22-27
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• 2004

Cisplatin is a highly effective and extensively used anticancer drug. Higher doses of cisplatin manifest acute nephrotoxicity and this is one of the limiting factors of this drug in cancer chemotherapy. The effect of the oyster mushroom extract to ameliorate cisplatin ( cis platinum (II) diammine dichloride) induced nephrotoxicity and restoration of antioxidant defence system in mice was investigated. The investigations showed that prior administration of methanolic extract of Pleurotus florida at a dose of 500 and 1000mg/Kg body weight significantly reduced elevated serum creatinine and urea levels and increased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the kidney, consequent to cisplatin treatment, in a dose dependent manner. The extract restored the decreased reduced glutathione (GSH) activity and increased malondialdehyde (MDA) level due to cisplatin administration. The results thus indicated that oyster mushroom extract rendered significant protection against cisplatin induced nephrotoxicity and depletion of antioxidant defence system in a dose dependent manner. Since oyster mushrooms are excellently edible and non-toxic, the finding reported here is of significant use in cancer chemotherapy.

• Journal of Life Science
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• v.23 no.12
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• pp.1428-1435
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• 2013

The aim of this study is to investigate the melanogenic effect of Oenanthe javanica ethanolic extracts (OJE) containing quercetin and kaempferol in melanoma cells (B16F1). In order to determine whether OJE inhibits melanin synthesis at the cellular level, the melanoma cells were cultured in the presence of different concentrations of OJE. In the present study, the antioxidant effects of OJE on DPPH radical scavenging, power reduction, lipid peroxidation, and DNA oxidation were evaluated in a cell free system. Furthermore, the effect of OJE on the production of melanin was determined by dopaquinone (DOPA) assay and tyrosinase activity. In addition, the protein expression of tyrosinase, as well as antioxidant enzymes such as superoxide dismutase (SOD)-1, SOD-2 and glutathione reductase (GSH), were examined using Western blot analysis. In this study, it was observed that OJE exhibited an inhibitory effect on lipid peroxidation and blocked the DNA oxidation induced by the hydroxyl radical produced by Fenton's reagent. OJE increased melanin synthesis above 50 ${\mu}g/ml$ and tyrosinase activity was detected above 50 ${\mu}g/ml$. In Western blot analysis, OJE increased the expression levels of tyrosinase, SOD-1, SOD-2, and GSH in a dose-dependent manner. These findings indicate that OJE with antioxidant activity can regulate the tyrosinase activity and melanin production in melanocyte, suggesting that it could promote the development of black hair as well as protect skin from oxidative stress.

• Journal of Life Science
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• v.20 no.11
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• pp.1595-1602
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• 2010

Oxidation of low density lipoprotein (LDL) has been recognized as an important role in the initiation and progression of atherosclerosis. In this study, effects of allylmercaptan, a major metabolite compound of garlic, was studied on endothelial cell injury induced by oxidized low density lipoprotein (ox-LDL). The antioxidative activity of allylmercaptan was investigated by monitoring a thiobarbituric acid substance (TBARS). Allylmercaptan inhibited LDL oxidation induced by $Cu^{2+}$ at concentrations of 0.1, 1 and 10 mM in a dose dependent manner. Lactate dehydrogenase (LDH) release, as an index of cell injury, and intracellular glutathione levels were determined. Pulmonary artery endothelial cells were preincubated with allylmercaptan at $37^{\circ}C$ and 5% $CO_2$ for 24 hr, washed, and then exposed to 0.1 mg/ml oxidized LDL for 24 hr. Preincubation of endothelial cells with allylmercaptan significantly prevented the LDH release and depletion of GSH. Peroxides were measured directly in 24 well plates using a fluorometric assay. Allylmercaptan inhibited release of peroxides induced by ox-LDL in pulmonary artery endothelial cells. In a free system, allylmercaptan was shown to scavenge hydrogen peroxide. The data indicate that allylmercaptan can protect pulmonary artery endothelial cells from injury caused by oxidized LDL, and suggest that allylmercaptan may be useful for the prevention of atherosclerosis.

• The Journal of Internal Korean Medicine
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• v.35 no.2
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• pp.208-221
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• 2014

Purpose : Banhasasim-tang (BHSST) has been applied for treating the symptom of gastric stuffiness, which is similar to dyspepsia. The object of this study was to observe the healing effect of BHSST on the indomethacin (IND)-induced gastric ulcer in rats. Methods : Three different dosages of BHSST (400, 200 and 100 mg/kg) were orally administered 30 min before IND treatment; 6 hrs after IND treatment, the changes on the gross lesion scores, fundic histopathology, myeloperoxidase (MPO) activity, lipid peroxidation and antioxidant defense system (glutathione contents, catalase (CAT) and superoxide dismutase (SOD) activities) were observed, and compared with the activity of the synthetic anti-ulcer drug, a representative proton pump inhibitor omeprazole (OME) 10 mg/kg. Results : All three different dosages of BHSST treatment in the IND-induced gastric ulcer rats, significant and dose dependent decreased gastric damages - hemorrhagic gross lesions, gastric mucosa MPO levels and histopathological gastric ulcerative lesions - were detected as compared with the IND treated control rats. BHSST also strengthened the antioxidant defense systems - decreased the level of lipid peroxidation and CAT activity but increased the level of GSH and SOD activity, and BHSST 200 mg/kg showed similar anti-ulcerative effect as compared with OME 10 mg/kg. Conclusions : The results obtained in this study suggest that BHSST has favorable effects against IND-induced gastric damages, through significant and dose-dependent decreasing gastric damages and the strengthening of the body's antioxidant defense systems with direct anti-inflammatory effects.

• Toxicological Research
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• v.16 no.1
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• pp.1-8
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• 2000

Astrocytes generate free radicals including nitric oxide (NO) and reactive oxygen intermediates(ROI) which in turn play roles in the pathogenesis of degenerative diseases and sclerotic changes of the brain. This study was designed to evaluate the mechanism that free radicals contribute to the cytotoxicty of rat neonatal primary astrocytes. Treatment with NO donors alone including soldium nitroprusside(SNP), S-nitrosoglucathinoe (GSNO), and S-nitroso-n-acetylpenicillamine (SNAP) showed a little effect on the death of rat neonatal primary astrocytes, whereas SNP markedly induced the death of RAW 264.7 cells. ROI inculding H2O2 and O2 donor also slightly induced the death of rat primary astrocytes. However, 3-morpholinosydnonimine(SIN-1), a donor of peroxynitrite (ONOO), which is a reactive compound of NO with superoxide, significantly decreased the viability of rat primary astrocytes in a dose-dependent manner. Cells were retarded in outgrowth of viability of cellular processes with cell shrinkage and detachment from culture dishes. Hoechst staining demonstrated that SIN-1-induced cell death might be due to an apoptosis which was characterized by nuclear condensation and fragmentation. SIN-1-induced apoptosis was prevented by the pretreatment with superoxide dismutase (SOD) and catalase in rat primary astorocytes. Furthermore, prevention of the generation of reduced glutathione (GSH) by DL-buthionine-[S, R]-sulfoximine (BSO) aggravated the cytotoxic effects of SNP, benzene triol, and SIN-1 in rat primary astrocytes. Taken together, it is suggested that peroxynitrite may be a major effector of apoptosis and cellular antioxidant system is important for cell survival in rat prima교 astrocytes.

• Toxicological Research
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• v.23 no.2
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• pp.143-150
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• 2007

Although animal and epidemiological studies have suggested oxidative stress as an etiological factor in pathogenesis including cancer, inflammation, sepsis, fibrosis, cardiovascularlneurodegenerative diseases and aging-related disorders, conflicting results have been obtained in clinical trial with antioxidants. The reason for this discrepancy remains unknown but may be due, in part, to the lack of a validated assay system for evaluating antioxidant capacity. The antioxidant activity of a series of sugar alcohols against peroxyl radicals, hydroxyl radicals and peroxynitrites was determined by the total oxy-radical scavenging capacity (TOSC) assay and cell-based assay using H4IIE cells. Specific TOSC values calculated from the slope of the linear regression for erythritol, xylitol, sorbitol or mannitol against peroxyl radicals was $2.1{\pm}0.2,\;3.7{\pm}0.3,\;9.1{\pm}0.3$ or $8.7{\pm}1.1$ TOSC/mM, respectively. Specific TOSC values for erythritol, xylitol, sorbitol or mannitol against peroxynitrite was $1.9{\pm}0.3,\;3.9{\pm}0.4,\;7.8{\pm}0.7$ or $7.7{\pm}0.5$ TOSC/mM, respectively. These results suggest that oxy-radical scavenging capacity is dependent on the number of aliphatic hydroxyl group in sugar alcohols of monosaccharide. Tert-butylhydroperoxide (t-BHP)-induced cell toxicity determined by MTT assay was marginally attenuated by 10 mM erythritol, but completely inhibited by 10 mM xylitol, 2 mM sorbitol or 0.75 mM maltitol, a disaccharide alcohol. Oxidative stress markers, such as glutathione (GSH) and malondial-dehyde (MDA) levels, were measured in t-BHP-treated cells using HPLC equipped with a fluorescence detector and a reverse phase column. Erythritol did not change the levels of GSH and MDA in H411E cells treated with t-BHP. The t-BHP-induced changes in cellular GSH and MDA levels were ameliorated by 10 mM xylitol and completely blocked by 10 mM sorbitol and maltitol. These results indicate that sugar alcohols protect cells against oxidative stress via scavenging oxy-radical and suggest that TOSC assay in conjunction with cell-based assay is a valid method for evaluating antioxidant capacity of natural and synthetic chemicals.

• Food Science and Preservation
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• v.11 no.3
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• pp.364-372
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• 2004

To investigate antioxidative effects of n-hexane fraction of Angelica acutiloba on the ethanol-induced hepatotoxicity of rats, Sprague-Dawley rats weighing 100 $\pm$ 20 g were divided into 5 groups; normal group(NOR), ethanol(10 mL/kg, 35$\%$) treated group(CON), n-hexane fraction of Angelica acutiloba 70 mg/kg treated group(Al), n-hexane fraction of Angelica acutiloba 70 mg/kg and ethanol treated group(A2) and n-hexane fraction of Angelica acutiloba 140 mg/kg and ethanol treated group(A3), respectively. The antioxidative activities of ethanol extract of Angelica acutiloba in vitro were decreased in order of n-hexane > ethylacetate > chlorofonn > n-butanol (>) water fraction. The growth rate and feed efficiency rate decreased by ethanol were gradually increased to the adjacent level of the normal group by administering n-hexane fraction of Angelica acutiloba. It was also observed that the activities of SOD of liver, ALT and AST of serum increased by ethanol were markedly decreased in n-hexane fraction of Angelica acutiloba administered group, and not in activites of XO, catalase, as compared with the control group. The depleted content of GSH by ethanol was increased adjacent to normal level by administering n-hexane fraction of Angelica acutiloba. as a dose-dependent manner. These results suggested that n-hexane fraction of Angelica acutiloba has a possible protective effect on the ethanol-induced hepatotoxicity of rats.