• BMB Reports
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• v.38 no.3
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• The Korean Journal of Food And Nutrition
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• v.22 no.2
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• pp.313-319
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• 2009

To improve the growth of human mesenchymal stem cells(hMSCs) under general cell culture conditions(20% $O_2$ and 5% $CO_2$), we examined the effect of s-allylcysteine(SAC), which is known as an antioxidant and the main component of aged-garlic extract, on hydrogen peroxide-induced cellular stress in hMSCs. We found that SAC blocked hydrogen peroxideinduced cell death and cellular apoptosis, but that SAC did not improve the growth of hMSCs during short-term culture. To evaluate the protective effect of SAC, we examined the endogenous expression of the antioxidant enzymes catalase (CAT), superoxide dismutase(SOD), and glutathione peroxidase(Gpx) in hMSCs. Hydrogen peroxide was found to downregulate the expression of CAT, SOD, and Gpx at the protein level. However, in the pre-treatment group of SAC, SAC inhibited the hydrogen peroxide-induced down-regulation of CAT, SOD, and Gpx. Unfortunately, treatment with SAC alone did not induce the up-regulation of antioxidant enzymes and the cell proliferation of hMSCs. Surprisingly, SAC improved cell growth in a single cell level culture of hMSCs. These results indicate that SAC may be involved in the preservation of the self-renewal capacity of hMSCs. Taken together, SAC improves the proliferation of hMSCs via inhibition of oxidative-stress-induced cell apoptosis through regulation of antioxidant enzymes. In conclusion, SAC may be an indispensable component in an in vitro culture system of human MSCs for maintaining self-renewal and multipotent characterization of human MSCs.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.95-103
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• 2011

This study was performed to investigate the antioxidant mechanism of tomato wine with varying lycopene content in rats fed a high fat diet (HFD). Male Sprague-Dawley rats were randomly divided into five groups (n=10 per group) and fed an HFD (35% of total energy from fat) plus ethanol (7.2% of total energy from alcohol), tomato wine with varying lycopene content (0.425 mg%, 1.140 mg% or 2.045 mg% lycopene) or an isocaloric control diet for 6 weeks. Mice fed HFD plus ethanol significantly increased erythrocyte hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) levels with increases in activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) compared to pair-fed rats. Supplementation of tomato wine with varying lycopene content decreased ethanol-mediated increases of erythrocyte lipid peroxidation and antioxidant enzyme activities in HFD-fed rats, and tomato wine with higher lycopene appeared to be more effective. Tomato wine also dose-dependently lowered TBARS levels with decreased pro-oxidant enzyme, xanthine oxidase (XOD) activity in plasma of HFD-fed rats. In contrast to erythrocytes, the inhibitory effects of tomato wine on hepatic lipid peroxidation were linked to increased hepatic antioxidant enzymes (SOD and CAT) and alcohol metabolizing enzyme (alcohol dehydrogenase and aldehyde dehydrogenase) activities. There were no significant differences in hepatic XOD and cytochrome P450-2E1 activities among the groups. Together, our data suggest that tomato wine fortified with lycopene has the potential to protect against ethanol-induced oxidative stress via regulation of antioxidant or pro-oxidant enzymes and alcohol metabolizing enzyme activities in plasma, erythrocyte and liver.

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.273-282
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• 2009

Cadmium (Cd) and tributyltin (TBT) are common contaminants of marine and freshwater ecosystems, and can induce the formation of reactive oxygen species (ROS). These ROS can, in turn, cause oxidative stress. In the present study, we investigated time-related effects of Cd (0.05 and 0.1 ppm) and TBT (5 and 10 ppb) treatment on antioxidant enzyme activity, i.e., the activity of superoxide dismutase (SOD) and catalase (CAT) in the gills and digestive glands of the ark shell, Scapharca broughtonii. In addition, hydrogen peroxide ($H_2O_2$) concentrations, lysozyme activity, and glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were measured in the hemolymph. We found that Cd and TBT treatment significantly increased antioxidant enzyme mRNA expression and activity in the digestive glands and gills in a time-dependent manner. In response to the Cd and TBT treatments, antioxidant enzymes mRNA expression and activity increased up to day 5 in the digestive glands and then decreased by day 7. In the gills, antioxidant enzymes mRNA expression and activity increased up to day 3 and then decreased by day 5. Likewise, $H_2O_2$ concentrations significantly increased up to day 5 and then decreased by day 7. Finally, lysozyme activity decreased during the experimental period, whereas GOT and GPT levels were significantly increased in a time-dependent manner. These results suggest that antioxidant enzymes play an important role in decreasing ROS levels and oxidative stress in ark shells exposed to Cd and TBT.

• YAKHAK HOEJI
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• v.51 no.4
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• pp.285-290
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• 2007

The oxidative stress causes many diseases like cancer, aging, cardiovascular disease, degenerative neurological disorders (Parkinson’s disease, and Alzheimer's disease) by damage of cell membrane, protein deformation, and damage of DNA due to the oxidation of lipid of cell membrane, protein of tissue or enzyme, carbohydrate, and DNA. It is caused by the reactive oxygen species (ROS) that is produced in the metabolic process of oxygen in cell. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in cell systemize the antioxidative enzymes to control the oxidative stress. In this research, it is measured that the survival rate of cell by the typical isoflavonoid of daidzein or genistein, activity of antioxidative enzyme, and ROS level, in order to study the effect of isoflavonoid over the ROS production in cell and antioxidative system. As the similar action of the isoflavonoid with the estrogen is examined, women are encouraged to get bean. In view of this trend, it is very important to find out a combination medicine that lowers the oxidative stress caused by the daidzein in the ovarian cell. In the combined treatment of the typical antioxidant of vitamin C to oxidative stress which induced by daidzein recover the control level particularly lowering the ROS in cell by 30%. However, it made no effect in the combined treatment with genistein. Therefore, the research took the combination effect of daidzein with vitamin C in order to check it effect over the antioxidative system. In conclusion, it was disclosed that the oxidative stress caused by daidzein is related to the lowering activity of SOD, and the specific combination effect of daidzein with vitamin C is related to the recovery of SOD activity.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.38 no.5
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• pp.304-308
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• 2005

The effects of diethylhexyl phthalate (DEHP) on various oxidative stress responses in liver, kidney and gill tissues of freshwater bagrid catfish Pseudobagrus fulvidraco were investigated under laboratory conditions. Bagrid catfish were intraperitoneally injected with sunflower seed oil containing nominal concentrations of 0, 300 or 900mg DEHP per kilogram of body weight for 3 days and the effects after last injection were assessed in liver, kidney and gill tissues of the exposed organisms. The oxidative stress responses of fish were evaluated by analyzing the level of glutathione (GSH), as well as the activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR). After exposure to the DEHP, there were significant decrease in GR, GPx activity and GSH content in liver of fish exposed to 900 mg DEHP per kilogram of body weight compared to the control group. Compared with the control group, significant decreases in renal GPx and GR activity were observed in the DEHP treatment groups (900 mg $kg^{-1}$ bw). However, no significant difference was observed in any oxidative stress responses in gills between the DEHP-treated and the untreated group of fish. The findings of the present investigation show that DEHP induce oxidative stress and the liver was the most affected organ followed by the kidney and gills. Furthermore, the changes of GPx and GR activities may be important indicators of oxidative stress responses but additional study is required to confirm the oxidative stress of DEHP.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2004.04a
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• pp.3-10
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• 2004

Oxidative stress is a constant threat to all living organisms and an immense repertoire of cellular defense systems is being employed by most pro- and eukaryotic systems to eliminate or to attenuate oxidative stress. Ischemia and reperfusion is characterized by both a significant oxidative stress and characteristic changes in the antioxidant defense. Heme oxigenase-l (HO-l) is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against ischemic injury in mammalian cells. Higenamine, an active ingredient of Aconite tuber, has been shown to have antioxidant activity along with inhibitory action of inducible nitric oxide synthase (iNOS) expression in various cells. In the present study, we investigated whether higenamine and related analogs protect cells from oxidative cellular injuries by modulating antioxidant enzymes, such as HO-l, MnSOD etc. R-form of YS-51 was the most potent inducer of HO-l in bovine endothelial cells, which inhibited apoptotic cell death by H$_2$O$_2$. HO-1 induction by YS 51 was mediated by PI3 kinase activation in which PKA- as well as PKG pathway is considered as important regulators. YS-51 also induced Mn-SOD mRNA expression by activating c-jun N-terminal kinase in endothelial cells and Hela cells. In ROS 17/2.1 cells, higenamine and enetiomers of related compounds inhibited iNOS expression by cytokine mixtures. Taken together, higenamine and related compounds can be developed as possible protective agents from oxidative cell injury or death.

• Korean Journal of Acupuncture
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• v.25 no.1
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• pp.139-154
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• 2008

Objectives & Methods : The purpose of this study is to observe the anti-oxidative effects of electroacupuncture to Yinlingquan(SP9) in AAPH induced oxidative stress of rats. The author performed several experimental items including measurements of body weight, levels of albumin, total bilirubin, LDL-cholesterol, GOT and GPT in serum, levels of SOD, glutathione, catalase, NO and MDA in liver, histological analysis of liver. The conclusions are as follows. Results : 1. In the SP9-EA group, the level of LDL-cholesterol was significantly decreased in comparison with that of the holder group and control group. 2. In the SP9-EA group, SOD activity, glutathione concentration in liver were increased, and NO concentration was decreased significantly in comparison with those of the control group and the holder group. 3. In the SP9-EA group, the density of liver tissue was maintained more similarly to the normal group in comparison with those of the control group and the holder group. 5. The results of the SP9-NR group showed similar tendencies with those of the SP9-EA group, but the effects were lower than those of the SP9-EA group. Conclusion : These results suggest that electroacupuncture at SP9 has an anti oxidative effect through suppressing both the reduction of anti-oxidative enzymes and production of oxidized substances.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.199-205
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• 2004

Cytochrome P450 (P450) 1 enzymes such as P450 1A1, 1A2, and 181 are known to be involved in the oxidative metabolism of various procarcinogens and are regarded as important target enzymes for cancer chemoprevention. Previously, several hydroxystilbene compounds were reported to inhibit P450 1 enzymes and were rated as candidate chemopreventive agents. In this study, we investigated the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, on the activities of P450 1 enzymes. The inhibitory potential by DMPVT on the P450 1 enzyme activity was evaluated with the Escherichia coli membranes of the recombinant human cytochrome P450 1A1, 1A2, or 1B1 coexpressed with human NADPH-P450 reductase. DMPVT significantly inhibited ethoxyresorufin O-deethylation (EROD) activities with $IC_{50}$ values of 61, 11, and 2 nM for 1A1, 1A2, and 1B1, respectively. The EROO activity in OMBA-treated rat lung microsomes was also significantly inhibited by OMPVT in a dose-dependent manner. The modes of inhibition by DMPVT were non-competitive for all three P450 enzymes. The inhibition of P450 1B1-mediated EROD activity by OMPVT did not show the irreversible mechanism-based effect. The loss of EROD activity in P450 1B1 with OMPVT incubation was not blocked by treatment with the trapping agents such as glutathione, N-acetylcysteine, or dithiothreitol. Taken together, the results suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered as a good candidate for a cancer chemopreventive agent in humans.

• CELLMED
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• v.8 no.3
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• pp.12.1-12.7
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• 2018

The study was designed to assess antioxidant and antidyslipidaemic effects of terpenoid-rich extract from the root of Aristolochia ringens V. Hyperglycemia-induced oxidative stress and dyslipidemia were established in rats by single intraperitoneal administration of 65 mg/kg bw streptozotocin. Based on therapeutic dose determined in previous study, streptozotocin-induced rats were orally administered with 75 and 150 mg/Kg bw of A. ringens extract for 14 days. Total protein, serum lipid profiles and biomarkers of oxidative stress in liver and kidney of the experimental rats were determined. Atherogenic and cardiovascular disease risk indices were computed. Streptozotocin-induced hyperglycaemia significantly (p < 0.05) decreased activities of superoxide dismutase, catalase and glutathione transferase as well as the amount of reduced glutathione in both tissues indicating oxidative stress induced kidney and liver injury due to glucotoxicity. In comparison to non-treated hyperglycaemic rats, activities of the antioxidant enzymes and concentration of glutathione-H were significantly (p < 0.0001) increased, whereas malondialdehyde was reduced in the tissues of rats treated with both 75 and 150 mg/Kg bw of the extract. The extract also caused significant (p < 0.001) reduction in elevated levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol levels, whereas concentration of the attenuated high density lipoprotein-cholesterol was increased in serum of the treated rats. Reduced atherogenic and cardiac risk indices were projected for the A. ringens extract-treated groups. Results from this study showed that extract from A. ringens root was rich in terpenoids and may reduce risks of complications associated with hyperglycemia-induced oxidative stress and dyslipidemia.