• Title/Summary/Keyword: Oxidative damage

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The Scavenging Effect on Nitric Oxide in Carthami Flos Herbal-Acupunture Solution (홍화 약침액의 Nitric Oxide에 대한 소거효과)

  • Woo, Dong-Su;Lee, Kyung-Min;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul
    • Journal of Pharmacopuncture
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    • v.10 no.2 s.23
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    • pp.25-30
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    • 2007
  • Objectives : Free radical metabolism seems to occupy a remarkably common position in the mechanisms of aging and aging related disease. Oxidative damage to DNA, lipids. proteins and other molecules may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. This study was designed to find out whether Carthami Flos Herbal-Acupuncture Solution can scavenge Nitric Oxide(NO) or not. SNAP is NO generator. NO concentration was estimated after 2,6, 12 and 24 hrs in no treatment group, after treatment with Vit. C or 1, 10, 100${\mu}$g/m1 of Carthami Flos Herbal-Acupuncture Solution. There was no significant scavenging effect of Carthami Flos Herbal-Acupuncture Solutionon NO after 2 hrs. But there was a significant scavenging effect of Cafhami Flos Herbal-Acupuncture Solution on NO in 10${\mu}$/m1 group after 6hrs. And there was a significant scavenging effect of carthami Flos Herbal-Acupuncture Solution on NO in 1, 10${\mu}$g/ml group after 12, 24 hrs. These results suggest that Carhami Flos Herbal-Acupuncture Solution has scavenging effect on NO. This study shows that Carthami Flos Herbal-Acupuncture Solution can be used for aging related disease and further studies are required to investigate the antioxidative effects of it.

Cilostazol ameliorates diabetic nephropathy by inhibiting high-glucose-induced apoptosis

  • Chian, Chien-Wen;Lee, Yung-Shu;Lee, Yi-Ju;Chen, Ya-Hui;Wang, Chi-Ping;Lee, Wen-Chin;Lee, Huei-Jane
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.403-412
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    • 2020
  • Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

Neuroprotective Effects of Cambodian Plant Extracts on Glutamate-induced Cytotoxicity in HT22 Cells

  • Keo, Samell;Lee, Dong-Sung;Li, Bin;Choi, Hyun-Gyu;Kim, Kyoung-Su;Ko, Won-Min;Oh, Hyun-Cheol;Kim, Youn-Chul
    • Natural Product Sciences
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    • v.18 no.3
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    • pp.177-182
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    • 2012
  • Oxidative stress potentially induces neurotoxicity which is believed to underlie several major age-related diseases of the central nervous system. This study sought to identify the cytoprotective effects of sixty-nine Cambodian plants against glutamate-induced cell death. Cultured HT22 cells were applied as an in vitro model, and neurotoxicity was induced in these neuronal cells by exposure to a determined concentration of glutamate. Sixty-nine plant sources, as Cambodia's indigenous species, were purchased from O'reusey Market, Phnom Penh, and extracted with ethanol. These extracts were screened for cytoprotective effects against glutamate-triggered neurotoxicity in HT22 cells at concentrations of 100 and 300 ${\mu}g/ml$. Of these, eight ethanol extracts, bark of Anacardium occidentale, bark and sapwood of Bauhinia pulla, flowers of Borassus flabellifer, stems and leaves of Coix lacryma-jobi, bark and sapwood of Diospyros nitida, sapwood of Dipterocarpus obtusifolius, stems of Oryza rufipogon, and fruits of Phyllanthus emblica, showed significant cytoprotective effects against glutamate-induced cell damage and degeneration in HT22 cells.

Effects of Chelidonine on L-DOPA-Induced Cytotoxicity in PC12 Cells (Chelidonine이 PC12 세포내의 L-DOPA-유도 세포독성에 미치는 영향)

  • Kim, Yu-Mi;Lee, Jae-Joon;Jin, Chun-Mei;Yang, Yoo-Jung;Kang, Min-Hee;Lee, Myung-Koo
    • Korean Journal of Pharmacognosy
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    • v.34 no.3 s.134
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    • pp.242-245
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    • 2003
  • The effects of chelidonine, a benzophenanthridine isoquinoline alkaloid, on L-DOPA-induced cytotoxicity in PC12 cells were investigated. The treatment of PC12 cells with chelidonine $(1-4\;{\mu}M)$ decreased dopamine content in a dose-dependent manner (30.2% inhibition at $4\;{\mu}M)$. Chelidonine was not cytotoxic up to $4\;{\mu}M)$. However, chelidonine at concentrations higher than $5\;{\mu}M$ caused a cytotoxicity in PC12 cells. L-DOPA at concentrations higher than $50\;{\mu}M$ led to cell damage by oxidative stress in PC12 cells. Chelidonine at non-cytotoxic concentration ranges of $1-4{\mu}M$ aggravated L- DOPA $(20-50\;{\mu}M)$-induced cytotoxicity in PC12 cells. The L-DOPA-induced cytotocxicity was synergistically stimulated by chelidonine at concentrations grader than $5\;{\mu}M$. These data demonstrate that chelidonine exacerbates L-DOPA-induced cytotoxicity. Therefore, it is proposed that the long-term L-DOPA therapeutic patients with chelidonine may need to be checked for the adverse symptoms.

Protective Effect of Hwansodan in Serum and Glucose Deprivation Induced-apoptotic Death of PC12 Cells Via Ho-1 Expression (영양혈청 결핍성 PC12 세포고사에서 HO-1의 발현 증가를 통한 환소단의 보호 효과)

  • Jung, Jae-Eun;Kim, Jin-Kyung;Kang, Baek-Gyu;Park, Chan-Ny;Park, Rae-Kil;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1459-1466
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    • 2006
  • The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

Inhibition Effect on Neuro2A Cell by Apoptosis of Zizania latifolia Rhizoma (줄풀 줄기의 Neuro2A 신경세포고사에 대한 억제 효과)

  • Cha Yun-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.149-155
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    • 2006
  • To prevent human body injury from oxidative stress, antioxidants are very important and many research about antioxidants are generally being conducted. Hydrogen peroxide($H_2O_2$) that is one of vitality oxygen species has been seen that cause various diseases, DNA damage and gene change. The purpose of this study was to examine the inhibition effect of Zizania latifolia Rhizoma on apoptosis induced by $H_2O_2$ in Neuro2A cell. Neuro2A cells were cultivated in RPMI(GibcoBRL) with 5% FBS and treated with $H_2O_2$ and Zizania latifolia Rhizoma. We measured the cell viability and analyzed DNA fragmentation. Activity of PARP, Cytochrome C, caspase-9, caspase-3, p53, p21, Bax and Bcl-2 in the cell was examined dy using western blot. The results obtained were as Follows: The cell viability in Zizania latifolia Rhizoma treatment (60ug/ml<) decreased significantly compared with that of none treatment. (P<0.001) Zizania latifolia Rhizoma increased cell viability about twice as much as that being injury by $H_2O_2$. (Zizania Latifolia Rhizoma 20ug/ml, $H_2O_2$ 200uM, P<0.001) DNA fragmentation developed by $H_2O_2$, but was not developed in Zizania latifolia Rhizoma treatment. PARP, Cytochrome C, caspase-9 and caspase-3 activated all by $H_2O_2$ but were not activated in Zizania latifolia Rhizoma treatment. P53, P2l and Bax activated dy $H_2O_2$, and Bcl-2 got into inactivation. But the opposite results appeared in Zizania latifolia Rhizoma treatment. In conclusion, these results suggest that Zizania latifolia Rhizoma inhibit the development of DNA fragmentation and apoptosis by $H_2O_2$ and the antioxidant action of Zizania latifolia Rhizoma is effective. More researches about effect of Zizania latifolia Rhizoma are considered to need.

Influence of Lead on Repetitive Behavior and Dopamine Metabolism in a Mouse Model of Iron Overload

  • Chang, JuOae;Kueon, Chojin;Kim, Jonghan
    • Toxicological Research
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    • v.30 no.4
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    • pp.267-276
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    • 2014
  • Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

Whole Brain Radiation-Induced Cognitive Impairment: Pathophysiological Mechanisms and Therapeutic Targets

  • Lee, Yong-Woo;Cho, Hyung-Joon;Lee, Won-Hee;Sonntag, William E.
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.357-370
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    • 2012
  • Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

Metabolic engineering for biofortification of lipophilic antioxidants in plants (식물의 지용성 항산화 물질 생산 증대를 위한 대사공학 연구현황)

  • Kim, Eun-Ha;Lee, Kyeong-Ryeol;Kim, Jong-Bum;Roh, Kyung Hee;Kang, Han Chul;Kim, Hyun Uk
    • Journal of Plant Biotechnology
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    • v.41 no.4
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    • pp.169-179
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    • 2014
  • Intracellular antioxidants include low molecular weight scavengers of oxidizing species, and enzymes which degrade superoxide and hydroperoxides. Such antioxidants systems prevent oxidative damage to cellular component by scavenging free radicals and activated oxygen species. Hydrophobic scavengers are found in cell membrane where they interrupt chain reactions of lipid peroxidation. The three major lipophilic antioxidant classes for human health are carotenoids, vitamin E and coenzyme Q10. The biofortification of staple crops with these lipid soluble antioxidants is an attractive strategy to increase the nutritional quality of human food. Here, we have summarized the biosynthetic pathways of three lipid soluble antioxidants in plants and current status of genetic engineered plants for elevated levels of each lipophilic antioxidant.

Synergistic Effect of Methanol Extract from Kalopanax pictus and Ascorbic Acid on Antioxidant, Anticancer and Immunomodulatory Activities (음나무(Kalopanax pictus) 추출물과 비타민 C의 항산화, 항암 및 면역활성 상승효과)

  • Shon, Mi-Yae
    • Journal of Life Science
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    • v.17 no.12
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    • pp.1634-1640
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    • 2007
  • The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), nitric oxide (NO) scavenging activities and ferric- reducing/antioxidant power (FRAP) assay against extracts of Kalopanax pictus (KP) were measured. Radical scavenging and antioxidant activities were increased depend on the concentration and the effects were enhanced by ascorbic acid (AA). KP extracts and AA had a good anti-proliferating activity against HepG2 cells by MTT assay and induces cells apoptosis, which was demonstrated by flow cytometric analysis. KP extracts and AA caused the arrest of cell-cycle progression at either G0-G1-phase or G2/M-phase, which might be depending upon the KP extracts concentration. In addition, KP extracts and AA are effective in enhancing immunity and nitric oxide production by RAW 264.7 macrophages cells. KP extracts and AA inhibited tumor cell growth and exerted antioxidant effects as compared to controls. These results demonstrate that simultaneous AA and KP extracts treatment could be useful in preventing the oxidative damage and anti-proliferating HepG2 cells, and are effective in enhancing immunomodulatory and antioxidant activity.