• Title/Summary/Keyword: Radical Mediator

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Transduction of Tat-Superoxide Dismutase into Insulin-producing MIN6N Cells Reduces Streptozotocin-induced Cytotoxicity

  • Choung, In-Soon;Eum, Won-Sik;Li, Ming-Zhen;Sin, Gye-Suk;Kang, Jung-Hoon;Park, Jin-Seu;Choi, Soo-Young;Kwon, Hyeok-Yil
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.3
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    • pp.163-168
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    • 2003
  • The reactive oxygen species (ROS) are considered to be an important mediator in pancreatic ${\beta}$ cell destruction, thereby triggering the development of insulin-dependent diabetes mellitus. In the present study, HIV-1 Tat-mediated transduction of Cu,Zn-superoxide dismutase (SOD) was investigated to evaluate its protective potential against streptozotocin (STZ)-induced cytotoxicity in insulin-producing MIN6N cells. Tat-SOD fusion protein was successfully delivered into MIN6N cells in a dose-dependent manner and the transduced fusion protein was enzymatically active for 48 h. The STZ induced-cell destruction, superoxide anion radical production, and DNA fragmentation of MIN6N cells were significantly decreased in the cells pretreated with Tat-SOD for 1 h. Furthermore, the transduction of Tat-SOD increased Bcl-2 and heat shock protein 70 (hsp70) expressions in cells exposed to STZ, which might be partly responsible for the effect of Tat-SOD. These results suggest that an increased of free radical scavenging activity by transduction of Tat-SOD enhanced the tolerance of the cell against oxidative stress in STZ-treated MIN6N cells. Therefore, this Tat-SOD transduction technique may provide a new strategy to protect the pancreatic ${\beta}$ cell destruction in ROS-mediated diabetes.

Antioxidant Effect of Bee Venom Herbal Acupuncture (봉독약침액의 항산화 효능)

  • Seo, Jung-Chul;Leem, Kang-Hyun;Han, Sang-Won
    • Journal of Pharmacopuncture
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    • v.6 no.1
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    • pp.67-72
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    • 2003
  • Bee venom has been clinically used to control the pain of inflammation disease etc. in general. Although the effect of bee venom herbal acupuncture has been reported, its mechanism has not been fully elucidated yet. Free radical metabolism seems to occupy a remarkably common position in the mechanisms of inflammation and ageing related disease. Oxidative damage to DNA, lipids, proteins and other molecules may contribute to the development inflammation disease. NO or DPPH is one of the free radicals and a mediator in inflammation diseases. The objective of this study is to investigate the scavenging effect of bee venom herbal acupuncture against NO and DPPH. The followings are the summary of the results: (1) There is no significant scavenging effect of bee venom herbal acupuncture on NO in BVS and BVP group. (2) There is a significant scavenging effect of bee venom herbal acupuncture on DPPH in BVS-1 and BVP-1 group. These results suggest that bee venom herbal acupuncture can be used for inflammation diseases such as rheumatoid arthritis. This study would provide important basic data on the possibility of the clinical treatment of bee venom herbal acupuncture. Further studies are required to investigate the antioxidative effects of it.

Hydrogen Peroxide Induces Apoptosis of BJAB Cells Due to Formation of Hydroxyl Radicals Via Intracellular Iron-mediated Fenton Chemistry in Glucose Oxidase-mediated Oxidative Stress

  • Lee, Jeong-Chae;Son, Young-Ok;Choi, Ki-Choon;Jang, Yong-Suk
    • Molecules and Cells
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    • v.22 no.1
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    • pp.21-29
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    • 2006
  • The aim of this study was to determine if hydrogen peroxide ($H_2O_2$) generated by glucose oxidase (GO) induces apoptosis or necrosis of BJAB cells and which radical is the direct mediator of cell death. We found that GO produced $H_2O_2$ continuously in low concentrations, similar to in vivo conditions, and decreased proliferation and cell viability in a dose-dependent manner. The GO-mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the cells after H33342/Annexin V/propidium iodide staining. Decreases of mitochondrial membrane potential and intracellular glutathione level were found to be critical events in the $H_2O_2$-mediated apoptosis. Additional experiments revealed that $H_2O_2$ exerted its apoptotic action through the formation of hydroxyl radicals via the Fenton rather than the Haber-Weiss reaction. Moreover, intracellular redox-active iron, but not copper, participated in the $H_2O_2$-mediated apoptosis.

Effects of Interleukin-$1\beta$, Tumor Necrosis Factor-$\alpha$ and Interferon-$\gamma$ on the Nitric Oxide Production and Osteoclast Generation in the Culture of Mouse Bone Marrow Cells

  • Kwon, Young-Man;Kim, Se-Won;Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.31 no.2
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    • pp.67-72
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    • 2006
  • Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of $30{\mu}M$ SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration($3{\mu}M$) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

The Study on Pharmacological Activation as Cosmetic Material of Rosa rugosa Thunb. Flowers Extract (해당화꽃 추출물의 화장품소재로서 약리활성에 관한 연구)

  • Yu, Hye-Soo;Choi, Ji-Eun;Woo, Won-Hong;Mun, Yeun-Ja
    • Korean Journal of Acupuncture
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    • v.31 no.4
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    • pp.188-194
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    • 2014
  • Objectives : In this study, we investigated the effect of ethanol extract from Rosa rugosa Thunb. flowers(ERF) on the activities of antioxidant, antiwrinkle and whitening. Methods : We measured antioxidant efficacy of ERF by using 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay. Also we confirmed the inhibitory effect of ERF on collagenase activity and melanin synthesis by using collagenase assay kit and dihydroxiphenylalanine staining, respectively. To evaluate the anti-inflammatory effects of ERF, we examined the inflammatory mediator IL-6. Results : ERF showed highly efficacy in DPPH radical scavenging activity. ERF dose-dependently suppressed collagenase activity. Ultraviolet-induced production of IL-6 decreased by ERF treatment. In B16F10 cell, ERF significantly reduced tyrosinase activity and melanin synthesis. Conclusions : From the above results, it was indicated that ERF could be utilized as anti-aging and whitening cosmetic ingredients.

Another Evidence for Nitric Oxide as Mediator of Relaxation of Isolated Rabbit and Human Corpus Cavernosum

  • Chang, Ki-Churl
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.136-140
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    • 1994
  • To prove the hypothesis that NO- and N $O_2$-carrying molecules potentiate photorelaxation by generating NO, investigation was carried out using isolated rabbit and human corpus cavernosum. Corporal smooth muscle, in the presence or absence of endothelium, relaxed only slightly upon ultraviolet light (366 nm) irradiation. But, NO-and/or N $O_2$-containing compounds such as streptozotocin and $N^{G}$-nitro-L-arginine methyl ester significantly (p<0.01) enhanced photorelaxation in this tissue. In addition, $N^{G}$-nitro-D-arginine methyl ester, known to lack inhibitory action on NO synthase, showed concentration-dependent potentiation of the photorelaxation. Oxygen radical generating system via copper+ascorbic acid and guanylate cyclase inhibitor, methylene blue, significantly (p<0.05) inhibited the streptozotocin-potentiated photorelaxation. Nitrite was accumulated by photolysis of streptozotocin, $N^{G}$-nitro-L-arginine methyl ester and $N^{G}$-nitro-D-arginine methyl ester, in a concentration and exposure time dependent manner. These observations indicate that NO is a potent relaxant of rabbit and human corpus cavernosum and further support the hypothesis that NO is released by photolysis from NO- and N $O_2$-carrying molecules.lecules.

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Inhibition of Human Neutrophil Elastase by Tetracyclines and Mechanism of the Inhibition (Tetracycline계 항균제에 의한 호중구 Elastase의 효소 활성도 억제 및 그 작용 기전)

  • Kim, Woo-Mi;Kang, Koo-Il
    • The Korean Journal of Pharmacology
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    • v.29 no.1
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    • pp.131-137
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    • 1993
  • Human neutrophil elastase (HNE, EC 3,4,21, 11), a mediator of tissue breakdown, was inhibited by tetracycline, oxytetracycline and demeclocycline. Among them, oxytetracycline showed the most potent inhibitory effect on the activity of HNE. IC50 of this drug at our specific condition was less than 1 mM. Tetracycline inhibited human neutrophil elastase non-competitively, and oxytetracycline inhibited competitively. Ki values of tetracycline and oxytetracycline were 4.9 mM and 0.39 mM, respectively. Structural modified tetracycline, de-dimethylaminotetracycline, which showed no antibiotic activity since the active dimethylamino radical was removed from the position #4 of the tetracycline, showed similar inhibition effect on the activity of human neutrophil elastase to that of tetracycline. Thus, we speculated that inhibition of human neutrophil elastase by tetracyclines was not depended on the dimethylamino radical which is a critical active site for antibiotic effect, rather it was depended on the hydoxyl radical of tetracyclines. Therefore, the property of inhibiting elastase may be an additional molecular biochemical mechanism of action of these drugs at the inflammatory sites.

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Determination of levels of nitric oxide in smoker and nonsmoker patients with chronic periodontitis

  • Wadhwa, Deepti;Bey, Afshan;Hasija, Mukesh;Moin, Shagufta;Kumar, Arun;Aman, Shazia;Sharma, Vivek Kumar
    • Journal of Periodontal and Implant Science
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    • v.43 no.5
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    • pp.215-220
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    • 2013
  • Purpose: Cigarette smoking is a major risk factor in periodontal diseases. The pathogenesis of periodontal diseases may be affected by alterations of the inflammatory response by smoke. Nitric oxide (NO) is a gaseous, colorless, highly reactive, short-lived free radical with a pivotal role in the regulation of various physiological and pathological mechanisms in the body. It is important in host defense and homeostasis, on the one hand, whereas, on the other hand, it modulates the inflammatory response in periodontitis, leading to harmful effects. The aim of this study was to assess the levels of NO in both the serum and saliva of smokers and nonsmokers having chronic periodontitis and to compare them with periodontally healthy controls. Methods: Sixty subjects participated in the study and were divided into three groups: group I, healthy nonsmoking subjects; group II, nonsmoking patients with chronic periodontitis; group III, smoking patients with chronic periodontitis. Each group consisted of twenty subjects. The biochemical estimation of NO in the collected serum and in the saliva was performed using the Griess colorimetric reaction. Results: The results showed that the mean value of the salivary and serum NO was greater in group II than in group I, and also greater in group III than in group II. Conclusions: NO appears to play an important and rather complex role in the immuno-inflammatory process and in the remodeling and maintenance of osseous structures. It is therefore logical that modulation of this mediator has potential for the treatment of a number of inflammatory conditions including periodontal disease.

Antioxidant and Anti-inflammatory Effect of Angelica Tenuissima in IFN-${\gamma}$/LPS-stimulated Peritoneal Macrophage (IFN-${\gamma}$와 LPS로 자극된 쥐의 복강 대식세포에서 고본(藁本) 메탄올 추출물의 항염증 효과)

  • Lee, Se-Yeoun;Park, Ho-Jun;Cha, Dong-Seok;Shin, Tae-Yong;Na, Ho-Jeong;Moon, Woo-Sung;Kang, Yang-Gyu;Jeon, Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1549-1556
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    • 2008
  • The objective of this study were to evaluate the antioxidant activity and the anti-inflammatory effects of Angelica tenuissima (AT) which has been used widely as a traditional medicine. The antioxidant activities of AT was tested by DPPH radical scavenging, superoxide anion scavenging and nitric oxide scavenging. AT showed strong antioxidant activity in all experiment. In macrophages nitric oxide (NO) is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions and high concentratin of NO is produced by inducible nitric oxide synthase (iNOS). In this study we have examined the inhibition effects of NO by 85% methanol extracts of AT in mouse (C57BL/6) peritoneal macrophage. AT (100, 1000 ${\mu}g/m{\ell}$) suppressed nitric oxide production and iNOS expression without any notable cytotoxicity and it also inhibited the expression of inflammatoryenzymes like cyclooxygenase-2 (COX-2). These data suggest that 85% methanol extracts of AT may possibly be used as antioxidant and anti-inflammatory agent.

Leukocyte Sequestration and Free Radical-Mediated Lung Injury in Ovine Cardiopulmonary bypass Using Membrane Oxygenator (양에서 막형 산화기를 사용하여 심폐바이패스할 경우 백혈구격리 및 자유라디칼로 중재되는 폐손상)

  • 김원곤;신윤철;서정욱
    • Journal of Chest Surgery
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    • v.32 no.11
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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.

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