• Progress in Medical Physics
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• 제11권2호
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• pp.157-165
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• 2000

Purpose: For estimation of yields of l)NA damages induced by radiation and enhanced by oxygen, a mathematical model was used and tested. Materials and Methods: Reactions of the products of water radiolysis were modeled as an ordinary time dependant equations. These reactions include formation of radicals, DNA damage, damage repair, restitution, and damage fixation by oxygen and H-radical. Several rate constants were obtained from literature while others were calculated by fitting an experimental data. Sensitivity studies were performed changing the chemical rate constant at a constant oxygen number density and varying the oxygen concentration. The effects of oxygen concentration as well as the damage fixation mechanism by oxygen were investigated. Oxygen enhancement ratio(OER) was calculated to compare the simulated data with experimental data. Results: Sensitivity studies with oxygen showed that DNA survival was a function of both oxygen concentration and the magnitude of chemical rate constants. There were no change in survival fraction as a function of dose while the oxygen concentration change from 0 to 1.0 x 10$^{7}$ . When the oxygen concentration change from 1.0 $\times$ 107 to 1.0 $\times$ 101o, there was significant decrease in cell survival. The OER values obtained from the simulation study were 2.32 at 10% cell survival level and 1.9 at 45% cell survival level. Conclusion: Sensitivity studies with oxygen demonstrated that the experimental data were reproduced with the effects being enhanced for the cases where the oxygen rate constants are largest and the oxygen concentration is increased. OER values obtained from the simulation study showed good agreement for a low level of cell survival. This indicated that the use of the semi-empirical model could predict the effect of oxygen in cell killing.

• Journal of Chest Surgery
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• 제32권11호
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• pp.978-983
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• 1999

Background: Complement activation with transpulmonary leukocyte sequestration is considered a main mediator leading to ischemia-reperfusion lung(I-R) injury. We studied the role of leukocytes in the formation of I-R injury in ovine cardiopulmonary bypass(CPB) model with a membrane oxygenator. Material and Method: Five sheep were used. CPB circuitry consisted of a roller pump(American Optical Corp., Greenwich, CT, USA) and a membrane oxygenator(UNIVOX-IC, Bentley, Baxter Health Corp, Irvine, CA, USA). The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter a total CPB of 100 min was performed, followed by another 10 min of partial CPB. The CPB was discontinued and the animals were fully recovered. For measuring left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 min and 109 in after the start of CPB, and 30 min and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 min and 120 min after weaning. Plasma malondialdehyde(MDA) was checked before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. One to two grams of lung tissue were taken for water content measurement before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. Lung biopsy specimens were examined by light and electron microscopy. Result: Of 5 animals, 4 survived the experimental procedures. Of these, 3 animals survived on a long-term basis. No significant differences in transpulmonary gradients of leukocyte were found and no significant complement activation was expressed by C3a levels. MDA level did not show significant changes related to lung reperfusion despite an increase after the start of CPB. On both light and electron microscopic examinations, mild to moderate acute lung change was observed. Interstitial edema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Conclusion: These findings indicate that ischemia-repersusion lung injury may not be from complement activation-leukocyte sequestration but from another source of oxygen free radicals related to CPB.

• Korean Journal of Veterinary Research
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• 제42권2호
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• pp.153-162
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• 2002

For the induction of arthropathy, 5% hydrogen peroxide($H_2O_2$) was injected for 5 weeks into the intraarticular space of the New Zealand white rabbits to damage articular cartilage. Alginic acid of low molecular weight (2%) made from macromolecular alginate treated with enzyme was administered into articular space at the dose of 5 mg/kg twice a week for 3 and 6 weeks using 1 ml syringe and 26 G needle. Saline was injected for the control. Tissues surrounding the articulation were obtained for the measurements of superoxide dismutase(SOD) activity as a major antioxidant enzyme and malondialdehyde (MDA) as a lipid peroxidation level. Histopathologic examination on the surface of articular cartilage was carried out. Data showed that injection of hydrogen peroxide for 5 weeks had led to the induction of free radical damage and of articular cartilage change as confirmed by microscopic observation. The application of hydrogen peroxide caused a gradual increase in the SODs and MDA. These patterns were similar after 3 and 6 weeks of alginate treatment. Furthermore, microscopic examinations revealed that hydrogen peroxide caused flaking, fibrillation, fissuring, denudation, and hypocellularity in the articular surfaces. In conclusion, lipid peroxidation was demonstrated in the articular cartilage by the administration of hydrogen peroxide in the rabbit model. This lipid peroxidation could be caused by oxygen free radicals. The histologic and enzymatic correlations on lipid peroxidation in the articulation have provided a better understanding of arthropathy. It is possible to take advantage of these findings to evaluate effective alginate dosage more efficiently.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.270-276
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• 2013

Fucoxanthin is an important carotenoid derived from edible brown seaweeds and is used in indigenous herbal medicines. The aim of the present study was to examine the cytoprotective effects of fucoxanthin against hydrogen peroxide-induced cell damage. Fucoxanthin decreased the level of intracellular reactive oxygen species, as assessed by fluorescence spectrometry performed after staining cultured human HaCaT keratinocytes with 2',7'-dichlorodihydrofluorescein diacetate. In addition, electron spin resonance spectrometry showed that fucoxanthin scavenged hydroxyl radical generated by the Fenton reaction in a cell-free system. Fucoxanthin also inhibited comet tail formation and phospho-histone H2A.X expression, suggesting that it prevents hydrogen peroxide-induced cellular DNA damage. Furthermore, the compound reduced the number of apoptotic bodies stained with Hoechst 33342, indicating that it protected keratinocytes against hydrogen peroxide-induced apoptotic cell death. Finally, fucoxanthin prevented the loss of mitochondrial membrane potential. These protective actions were accompanied by the down-regulation of apoptosis-promoting mediators (i.e., B-cell lymphoma-2-associated ${\times}$ protein, caspase-9, and caspase-3) and the up-regulation of an apoptosis inhibitor (B-cell lymphoma-2). Taken together, the results of this study suggest that fucoxanthin defends keratinocytes against oxidative damage by scavenging ROS and inhibiting apoptosis.

• Korean Journal of Plant Resources
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• 제19권6호
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• pp.649-654
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• 2006

The objective of present study was to investigate the anti oxidative and hepatoprotective effects of tomato extracts. Total antioxidant capacity and total antioxidant response were 5.5 and $19.8{\mu}g$ Trolox equivalent per mg of tomato extract, respectively. DPPH radical scavenging activity of tomato extracts ($10mg\;ml^{-1}$) was 70% as compared to 100% by pyrogallol solution as a reference. The effect of the tomato extracts on lipid peroxidation was examined using rat liver mitochondria induced by iron/ascorbate. Tomato extracts at the concentration of $0.5mg\;ml^{-1}$ significantly decreased TBARS concentration. Tomato extracts prevented lipid peroxidation in a dose-dependent manner. The effect of the tomato extracts on reactive oxygen species (ROS) generation was examined using cell-free system induced by $H_2O_2/FeSO_4$. Addition of $1mg\;ml^{-1}$ of tomato extracts significantly reduced dichlorofluorescein (DCF) fluorescence. Tomato extracts caused concentration-dependent attenuation of the increase in DCF fluorescence, indicating that tomato extracts significantly prevented ROS generation in vitro. The effect of tomato extracts on cell viability and proliferation was examined using hepatocyte culture. Primary cultures of rat hepatocytes were incubated with 1mM tert-butyl hydroperoxide (t-BHP) for 90 min in the presence or absence of tomato extracts. MTT values by addition of tomato extracts at the concentration of 2, 10, and $20mg\;ml^{-1}$ in the presence of t-BHP were 13, 33 and 48%, respectively, compared to 100% as control. Tomato extracts increased cell viability in a dose-dependent manner. These results demonstrate that tomato extracts suppressed lipid peroxidation and t-BHP-induced hepatotoxicity and scavenged ROS generation. Thus antioxidant and hepatoprotective effects of tomato extracts seem to be due to, at least in part, the prevention from free radicals-induced oxidation, followed by inhibition of lipid peroxidation.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• Journal of Korean Neurosurgical Society
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• 제64권6호
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• pp.873-881
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• 2021

Objective : Peripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects. Methods : Thirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated. Results : Compared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group. Conclusion : Gallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.

• Journal of Nutrition and Health
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• 제40권2호
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• pp.111-117
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• 2007

This study was designed to investigate the effects of pyroligneous liquor on oxygen radicals and their scavenger enzymes in the liver of Cri/Bgi CD rats (7 rats per group). Male rats were fed a basic diet prepared in our Lab., PL-0 (Control), PL-1, PL-25, PL-50 and PL-75 groups were Prepared to be 0%, 1%, 25%, 50% and 75%with distilled water using pyroligneous liquor (35% of Choa Co. Ltd.), and were administrated orally for 8 weeks. Superoxide radical contents in liver mitochondria and microsomes were significantly decreased to 12-14%, 11-15%, respectively, in these PL-25 and PL-50groups compared with the control group. Hydroxyl radical content in mitochondria and microsomes were markedly decreased to 12-20% and 17%, respectively, in these PL-25 and PL-50% groups compared with the control group. Hydrogen peroxide content in mitochondria and microsomes were significantly decreased about 15-12% and 22-20% in liver of PL-25 and PL-50 groups compared with the control group. Mn-SOD and Cu/Zn-SOD activities in liver of PL-25 and PL-50 groups were remarkably increased to 15-25%, 11-16%, respectively, compared with the control group. GPx activities in mitochondria and microsomes were significantly increased in the liver of PL-25 and PL-50 groups compared with the control group. CAT activities in mitochondria and cytosol were significantly increased to 12-14%, 15-27%, respectively, in the liver of PL-25 and PL-50 groups compared with the control group. These results suggest that long term administration orally of 25 and 50% pyroligneous liquor may effectively inhibit the formation of oxygen free radicals, and also scavenger enzyme activities significantly increase through the administration orally.

• Journal of the Korean Society of Food Science and Nutrition
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• 제30권4호
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• pp.668-672
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• 2001

To investigate the oxygen free radical and alcohol metabolizing system in liver of rats fed diets with 30% ethanol extract of Lycium chinense (LCEE), Sprague-Dawley male rats weighing 225~235g have been fed a diet supplemented with 2% or 4% LCEE for a month. The rats fed LCEE supplemented diets gained less body weight compared with the control, and had no remarkable changes of liver function. In rats fed 2% LCEE supplemented diet, hepatic cytochrome P450 contents appeared to be increased, but catalase (204.88$\pm$20.06 $H_2O$$_2$nmoles/mg protein/min), and superoxide dismutase (13.18$\pm$0.74 Unit/mg protein) activities were significantly increased compared with control 120.28$\pm$26.99 $H_2O$$_2$nmoles/mg protein/min and 10.49$\pm$0.80 Units/mg protein). There was no difference in hepatic glutathione content, glutathione peroxidase, and glutathione-S-transferase ctivities between the rats fed LCEE suplemented diets and the control diet. On the other hand, hepatic alcohol dehydrogenase activity were not changed by LCEE feeding, but hepatic aldehyde dehydrogenase activities were significantly increased in rats fed both 2 and 4% LCEE diets(5.01$\pm$0.21 and 4.47$\pm$0.06 $\mu$moles NADPH/mg protein/min) compared with control (3.28$\pm$0.21 $\mu$moles NADPH/mg protein/min) and its Vmax value was 1.9 fold increased in rats fed 2% LCEE and 1.5 fold in those fed 4% LCEE compared with control. In conclusion, it is likely that rats receiving a diet supplemented with LCEE may have the oxygen free radicals and alcohol detoxication potential.

• Journal of Physiology & Pathology in Korean Medicine
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• 제21권5호
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• pp.1163-1169
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• 2007

Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse 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 efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.