• 약학회지
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• 제35권1호
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• pp.45-60
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• 1991

lonophores, uniquely, create specific pathways of ion permeability in model and cell membranes. Calcium-transporting ionophores of microbiological origin, such as A23187 and ionomycin, have been used as experimental tools to elucidate the physiological role of calcium as a second messenger in many cell types. These ionophores are believed to bypass the initial ligand-receptor step in the activation of cells by increasing membrane permeability to calcium. In this report, we shall discuss several naturally occurring substances that share some properties of calcium-ionophores, primarily concentrating on oxidized fatty acids. We have previously demonstrated that oxidized linoteic and arachidonic acids, obtained either by lipoxygenase catalysis or nonenzymatic processes, significantly promote calcium translocation in a two-phase partition model and modulate calcium-transporting function in the isolated sarcoplasmic reticulum vesicles obtained from mammalian hearts. We have also confirmed that calcium-ionophoric properties are due not to their general amphiphilic nature of certain lipids, but to distinct structural characteristics. Although there are some skeptical views on the occurrence of ionophores in higher organisms, increasing evidence suggests that membrane lipids or their derivatives may serve as physiological calcium-ionophores. Abnormal accumulation of lipid peroxidation products(particularly end products), however, may be associated with the general oxidative damages as seen in many pathological conditions.

• 대한본초학회지
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• 제28권6호
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• pp.79-86
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• 2013

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against ${\beta}$-amyloid ($A{\beta}_{25-35}$)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against $A{\beta}_{25-35}$-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated $A{\beta}_{25-35}$-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, $A{\beta}_{25-35}$-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of ${\gamma}$-glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against $A{\beta}_{25-35}$-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer's disease.

• Clinical and Experimental Reproductive Medicine
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• 제29권2호
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• pp.105-115
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• 2002

Objective : To evaluate the effects of the reactive oxygen species (ROS) generated with a xanthine (X) and xanthine oxidase (XO) system on sperm function, the change of sperm characteristics, lipid peroxidation, and DNA fragmentation in bovine spermatozoa. Materials and Methods: ROS were produced using a combination of 1000 uM X and 50 mU/ml XO. The ROS scavengers: superoxide dismu tase (SOD) (200 U/ml) and catalase (500 U/ml) were also tested. Spermatozoa were incubated for 2 hours in BWW medium with a combination of X-XO supplemented with or without ROS scavengers at $37^{circ}C$ under 5% $CO_2$ incubator. Sperm movement characteristics by CASA (computer-aided sperm analysis), HOST (hypoosmotic swelling test), Caionophore induced acrosome reaction, malondialdehyde formation for the analysis of lipid peroxidation, the percentage of DNA fragmentation using the method of TdT-mediated nick end labelling (TUNEL) by flow cytometry were determined after 2 hours incubation. Results: The action of ROS on bovine spermatozoa resulted in a decreased in capacity for sperm motility, Ca-ionophore induced acrosome reaction and membrane integrity, an increased in malondialdehyde formation and the percentage of sperm with DNA fragmentation. In the effects of antioxidant, catalase completely alleviated the toxic effects induced by the ROS in terms of sperm function and characteristics, however SOD exhibited no capacity to reduce the toxic effects. Conclusion: The ROS can induce significant damages to sperm functions and characteristics. The useful ROS scavengers can minimized the defects of sperm function and various damages of spermatozoa.

• BMB Reports
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• 제40권6호
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• 대한한방내과학회지
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• 제21권2호
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• pp.283-290
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• 2000

The purpose of this study is to examine the toxic effects caused by xanthine oxidase/hypoxanthine(XO/HX) and the effects of herbal extracts such as Jingansikpungtang(JST) and Gamijingansikpungtang(GJST) on the treatment of the toxic effects. For this purpose, experiments with the cultured nerve cells from the spinal motor neurons of new born mice were done. The results of these experiments were as follows. XO/HX, a oxygen radical-generating system, decreased the survival rate of the cultured cells on NR assay. MTT assay, the amount of neurofilaments and increased the amount of total proteinand increased the lipid peroxidation and the amount of LDH JST has the efficacy of increasing the amount of neurofilaments and total protein, and decreasing the lipid peroxidation and the amount of LDH, GJST has efficacy of increasing the amount of neurofilaments and total protein, and decreasing lipid peroxidation and the amount of LDH. From the above results, it is concluded that JST and GJST have marked efficacy as a treatment for the damages caused in the XO/HX mediated oxidative stress. And JST and GJST are thought to have certain pharmacologicall effects. Further clinical study of this pharmacological effects of JST and GJST should be complemented.

• Journal of Nutrition and Health
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• 제40권8호
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• pp.701-707
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• 2007

This study was to investigate lipid peroxidation, antioxidant enzyme activity and DNA damage after exercise, and the protective effect of garlic against exercise-induced oxidative stress. Male Sprague-Dawley rats(4 weeks old) were randomly divided into three groups of 6 rats each; control group(Con) without garlic and exercise, Ex group with exercise alone, and Ex-G group with 2% garlic and exercise. For 4 weeks, rats were given diets containing 15% corn oil and 1% cholesterol with or without garlic. The swimming was selected as a model for exercise performance. Rats swam for 40 min a day, for 5 days a week. Group Ex and Ex-G showed significant lowering in body weight gain and fat accumulation compared to control. No significant changes were observed in levels of plasma cholesterol and triglyceride among three groups, demonstrating that exercise and garlic had no effects on changes of blood lipid. This finding of blood lipid seems to be due to higher plant sterol content in corn oil. The DNA tail moment of lymphocytes showed greater tendency in Ex and Ex-G than in control, but garlic supplements failed to suppress DNA damages. Compared to control, Ex had higher plasma TBARS which was lowered to the control's level in Ex-G with 2% garlic supplementation(p<0.05). Ex-G led to a higher hepatic superoxide dismutase(SOD) activity than control and Ex(p<0.05). Activity of hepatic catalase was also increased in Ex-G, while in Ex it was significantly low(p<0.05). It seemed that TBARS levels were related to the activities of SOD and catalase, and that garlic contributed to increasing the enzyme activities and led to decrease of TBARS. These results demonstrate that lipid peroxidation and DNA damage occur as a consequences of oxidative stress after exercise, and that antioxidant defense against oxidative stress could be enhanced by garlic supplementation through the induction of antioxidant enzymes. However, further investigations should be done on the garlic effect on DNA damage.

• Nutritional Sciences
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• 제9권1호
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• pp.9-13
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• 2006

The differential effects of various fatty acids such as n-3 and n-6 types or degrees of unsaturation on the CYP2E1 induction and the production of lipid peroxidation (LPO) were investigated. The CYP2E1-transduced human hepatoma HepG2 cells (E47) were cultured in RPMI 1640 media containing different concentrations of various fatty acids up to 48 h incubation compared to 04 cells and CYP2E1-null cells. Treated fatty acids were linoleic acid (LA:n-6, C18:2), arachidonic acid (AA:n-6, C20:4) and docosahexaenoic acid (DHA:n-3, C22:6). The cell survival rate was decreased corresponding to the degree of unsaturation (LA>AA $\cong$DHA) and to LPO production in E47 and 04 cells. The four or five unsaturation degree of fatty acids, AA and DHA, caused time- and dose-dependent cell death in E47 cells but not as much as in C34 (without CYP2E1), suggesting an important role of CYP2E1 in the DHA mediated damage. In the levels of lipid peroxides (LPO), AA also elevated LPO by 3- and 5- fold compared to DHA or LA treated E47 cells. However, AA did not increase LPO until 48 h incubation in C34 cells. In conclusion, the polyunsaturated fatty acids induced CYP2E1 induction might be changed by the elevated levels of lipid peroxide (LPO) and oxidative stress through the connection of CYP2E1 and degrees of unsaturated fatty acids.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.112-120
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• 1999

The protective actions of ambroxol, rutin, glutathione and harmaline on oxidative damages of various tissue components were compared. The mechanisms by which they prevent oxidative tissue damages were explored. Lipid peroxidation of liver microsomes induced by combinations of $Fe^{2+}$ and ascorbate or $Fe^{+3}$, ADP and NADPH was inhibited by $50\; \muM$ of rutin, ambroxol, harmaline and glutathione. Ambroxol ($100\; \muM$) inhibited the degradation of hyaluronic acid by $Fe^{2+}$, $H_2O$_2$ and ascorbate, and it was greater than that of harmaline, whereas hyaluronic acid degradation was not prevented by rutin and glutathione. The compounds used ($100\; \muM$) did not protect the degradation of cartilage collagen by xanthine and xanthine oxidase. Rutin, glutathione and harmaline decreased the degradation of IgG by xanthine and xanthine oxidate, while ambroxol did not attenuate degradation of IgG. Glutathione showed a scavenging action on $H_2O_2$. The compounds all showed scavenging actions on hydroxyl radical. Ambroxol and harmaline exhibited quenching effects en singlet oxygen. In conclusion, ambroxol, rutin, glutathione and harmaline may exert protective effects differently on tissue components against oxidative attack depend on kind of tissue component and free radical.

• 대한한의학회지
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• 제36권4호
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• pp.42-55
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• 2015

Purpose: The object of this study is to observe the anti-ulcerative effects of BK-1202 (IGM), a mixed herbal formula consisting of 9 herbal drugs, which have been traditional Korean medicine for treating various digestive diseases, on indomethacin-induced gastric ulcer in rat. Methods: Three different doses of IGM extract (200, 100 and 50 mg/kg) were orally administered once 30 min before indomethacin treatment. Six hours after indomethacin treatment, changes in the gross lesion scores, fundic histopathology, MPO activity and antioxidant activities were observed. The results were compared with two reference groups treated with omeprazole (10 mg/kg), antioxidant and proton pump inhibitor, and DA-9601 (100 mg/kg), a standardized extract of the herb Artemisiaasiatica. Results: In all three doses of IGM extract, significantly decreased gastric damages were observed in the indomethacin-induced gastric ulcer rats, when compared with the indomethacin-treated control rats. IGM extracts also strengthened the antioxidative defense systems, decreasing the level of lipid peroxidation and catalase activity while increasing the superoxide dismutase and glutathione contents. IGM extracts showed similar anti-ulcerative effects to those shown by equal dose of DA-9601, and the effects of 50 mg/kg IGM extracts were comparable to those of 10 mg/kg omeprazole. Conclusion: The results obtained in this study suggest that IGM extract has favorable effects on the indomethacin -induced gastric damages by strengthening the antioxidative defense systems and enhancing anti-inflammatory effects.

• 동의생리병리학회지
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• 제26권5호
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• pp.679-686
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• 2012

This study was to elucidate the effects of Ukgan-san on the hyperthyroidism induced by sodium levothyroxine. Hyperthyroidisms were induced by continuous subcutaneous treatment of LT4, 0.3 mg/kg, once a day for 27days, and 1,500, 1,000 and 500 mg/kg of Ulkansan extracts were orally administered, once a day for 15 days from 12th LT4 treatment, and the changes on the body, thyroid gland, liver and epididymal fat pad weights, serum triiodothyronine(T3), thyroxine(T4), thyroid-stimulating hormone(TSH), asparte aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, hepatic lipid peroxidation(LPO), glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) activities were investigated with throid gland, liver and epididymal fat pad histopathological changes. The effects of Ukan-san extracts were compared with that of propyl thiouracil(PTU), a standard antithyroidic drug 10 mg/kg(intraperitoneally). 1,500 and 1,000 mg/kg of Ukan-san extracts reversed all LT4-induced hyperthyroidisms and these effects indicating their potential in the regulation of hyperthyroidism. Further, the Ukan-san extract normalized LT4-induced liver oxidative stresses, and also reduced liver damages and epididymal fat pad reducements suggesting its antioxidative and relative organ protective nature. However, nor favorable effects on LT4-induced hyperthyroidisms were detected in Ulkansan 500 mg/kg treated rats as compared with LT4 control rats in the present study. These effects of Ukan-san may help improvement of hyperthyroidisms and accompanied various organ damages.