• 제목/요약/키워드: Free radical scavengers

검색결과 75건 처리시간 0.025초

The Role of Oxygen Free Radicals and Phospholipase $A_2$ in Ischemia-reperfusion Injury to the Liver

  • Park, Mee-Jung;Cho, Tai-Soon;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • 제18권3호
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    • pp.189-194
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    • 1995
  • The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase $A_2$ inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase $A_2$ inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidiltion was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quina crine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome $P_{450}$ content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase $A_2$ are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion.

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내분비계 장애물질인 Bisphenol A의 free radical 생성을 통한 독성발현 (Cytotoxicity of Environmental Estrogenic Compound, Bisphenol A, via Generation of Free Radicals)

  • 안광현;김봉희
    • Environmental Analysis Health and Toxicology
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    • 제18권3호
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    • pp.175-182
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    • 2003
  • Bisphenol A shares similarities in structure, metabolism and action with DES, a known human teratogen and carcinogen. Bisphenol A, a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. The purpose of the this study was to evaluate the cytotoxicity, cell proliferation of bisphenol A In the presence of a rat liver S9 mix, contaning cytochrome P450 enzymes, and Cu (II). In the present study, Bisphenol A in combination with Cu (II) exhibited a enhancement in cytotoxicity which were inhibited by free radical scavengers. The content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with concentration of bisphenol A. Also, we examined the change of CuZn-SOD, Mn-SOD, catalase and GPx activities in the MCF-7 cells exposed to bisphenol A. The activities of CuZn-SOD, CPx, catalase were found to decrease with bisphenol A concentration. Meanwhile, the activity of Mn-SOD was unchanged. This indicated that elevated oxidative stress caused by imbalance between the production and removal of free radicals occurred in cells.

자귀나무 잎의 자유라디칼 소거 물질 (Free Radical Scavengers from the Leaves of Albizzia julibrissin)

  • 장규관;오현철;고은경;강기홍;박성은;오명훈;김윤철
    • 생약학회지
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    • 제33권1호통권128호
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    • pp.18-20
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    • 2002
  • Assay-guided fractionation of the methanol extract of the leaves of Albizzia julibrissin has furnished quercitrin (1) and afzelin (2) as the scavengers of DPPH radical. Quercitrin and afzelin showed scavenging activity of DPPH free radical with the $IC_{50}$ values of 17.3 and 71.5 ${\mu}M$, respectively.

Induction of DNA Breakage by the Hot-water Extracts of Fructus Chaenomelis (Chaenomeles sinensis Koehne)

  • Nam, Seok Hyun;Chon, Dae Jin;Kang, Mi Young
    • Journal of Applied Biological Chemistry
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    • 제43권3호
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    • pp.156-160
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    • 2000
  • The possible mechanism of the DNA strand breaking activity of the hot-water extract of Fructus Chaenomelis (dried fruit of Chaenomeles sinensis) in a closed circular duplex replica form DNA (RFI DNA) was studied through agarose gel electrophresis under various conditions. Induction of DNA strand scission by the hot-water extract of C. sinensis occurred in dose and time-dependent manners. $Cu^{2+}$ was indispensable for the induction of DNA strand breakage. Exogeneous chelating agents inhibited the DNA breaking activity, conforming the catalytic action of $Cu^{2+}$ on generation of free radicals responsible for oxidative damage. Antioxidant enzymes and some radical scavengers were used to investigate the major radical species triggering the DNA strand scission, demonstrating that a highest inhibitory activity was found in the presence of catalase, while less in the presence of tiron (a scavenger for superoxide radical), 2-aminoethyl-isothiuroniumbromide-HBr, cysteamine (scavengers for hydroxyl radical), and 1,4-diazabicyclo [2,2,2] octane (a scavenger for singlet oxygen) in decreasing order. The findings implied that oxygen radical species generated in presence of transition divalent cation during the oxidation of some compounds contained in the hot-water extract of C. sinensis is mainly responsible for inducing genotoxicity.

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In Vitro Free Radical and ONOO- Scavengers from Sophora flavescens

  • Jung, Hee-Jin;Kang, Sam-Sik;Hyun, Sook-Kyung;Choi, Jae-Sue
    • Archives of Pharmacal Research
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    • 제28권5호
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    • pp.534-540
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    • 2005
  • Activity-guided fractionation of the CH$_2Cl_2$-soluble fraction of the roots of Sophora flavescens furnished five 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scaveng ers: trans-hexadecyl ferulic acid (1) cis-octadecyl ferulic acid (2), trans-hexadecyl sinapic acid (3), (-)-4-hydroxy-3-methoxy-(6aR,11aR)-8, 9-methylenedioxypterocarpan (4) and desmethylanhydroicaritin (8), along with nine known inactive compounds: (-)-maackiain (5), xanthohumol (6), formononetin (7), (2S)-2'-methoxykurarinone (9), (2S)-3${\beta}$,7,4'-trihydroxy-5-methoxy-8-(${\gamma},{\gamma}$- imethylallyl )-flavanone (10), (2S)-7,4'-dihydroxy-5-methoxy-8- (${\gamma},{\gamma}$-dimethylallyl ) -flavanone (11), umbelliferone (12), kuraridin (13), and trifolirhizin (14). Compounds 1-4 and 8 exhibited DPPH free radical scavenging effects at IC$_{50}$ values of 33.01 ${\pm}$ 0.20, 57.06 ${\pm}$ 0.16, 39.84 ${\pm}$ 0.36, 35.83 ${\pm}$ 0.47, and 18.11 ${\pm}$ 0.04${\mu}$M, respectively. L-Ascorbic acid, when used as a positive control, exhibited an IC$_{50}$ value of 7.39 ${\pm}$ 0.01 ${\mu}$M. Compounds 1-4 and 8 also appeared to exert significant scavenging effects on authentic ONOO-, with IC$_{50}$ values of 5.76 ${\pm}$ 1.19, 15.06 ${\pm}$ 1.64, 8.17 ${\pm}$ 4.97, 1.95 ${\pm}$ 0.29 and 4.06 ${\pm}$ 2.41 ${\mu}$M, respectively. Penicillamine (IC$_{50}$= 2.36 ${\pm}$ 0.79${\mu}$M) was used as a positive control. In addition, compounds 2,4,6,8, and 10 were isolated from this plant for the first time.

DNA Cleavage Induced by the Reaction of Salsolinol with Cu,Zn-Superoxide Dismutase

  • Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
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    • 제28권12호
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    • pp.2329-2332
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    • 2007
  • Salsolinol, endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the oxidative damage of DNA induced by the reaction of salsolinol with Cu,Zn-SOD. When plasmid DNA incubated with salsolinol and Cu,Zn-SOD, DNA cleavage was proportional to the concentrations of salsolinol and Cu,Zn-SOD. The salsolinol/Cu,Zn-SOD system-mediated DNA cleavage was significantly inhibited by radical scavengers such as mannitol, ethanol and thiourea. These results indicated that free radicals might participate in DNA cleavage by the salsolinol/Cu,Zn-SOD system. Spectrophotometric study using a thiobarbituric acid showed that hydroxyl radical formation was proportional to the concentration of salsolinol and was inhibited by radical scavengers. These results indicated that hydroxyl radical generated in the reaction of salsolinol with Cu,Zn-SOD was implicated in the DNA cleavage. Catalase and copper chelators inhibited DNA cleavage and the production of hydroxyl radicals. These results suggest that DNA cleavage is mediated in the reaction of salsolinol with Cu,Zn-SOD via the generation of hydroxyl radical by a combination of the oxidation reaction of salsolinol and Fenton-like reaction of free copper ions released from oxidatively damaged SOD.

Uniconazole 및 Free Radical Scavenger처리가 양버즘나무의 $SO_2$ 피해경감에 미치는 효과 (Effect of Uniconazole and Free Radical Scavenger Treatments on Reduction of $SO_2$ Injury in Platanus occidentalis)

  • 조정희;구자형;최종명
    • 한국환경농학회지
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    • 제16권1호
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    • pp.14-18
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    • 1997
  • $SO_2$에 대한 양버즘나무의 내성을 증대시키고자 uniconazole, sodium benzoate 또는 ascorbic acid를 단용 또는 복합처리한 후 $SO_2$에 의한 가시피해정도, 엽록소함량 및 유리기 제거제로 활성산소의 독성을 중화시킬 수 있는 superoxide dismutase(SOD) 및 peroxidase(POD)의 활성변화를 조사하였다. Uniconazole처리에 의한 $SO_2$ 피해경감 효과는 SOD불활성제인 diethyldithiocarbamate(DDTC)를 다시 처리하므로써 가시피해가 증가하였고 SOD와 POD의 활성도 감소하였다. 유리기 제거제인 sodium benzoate와 ascorbic acid처리는 SOD나 POD 활성에 영향을 주지않으면서 $SO_2$의 피해를 경감시키고, DDTC의 $SO_2$피해증가 효과를 ascorbic acid 처리로 감소시킬 수 있었다. 이상의 결과로 미루어 uniconazole은 식물체내에서 산화방지물질의 역할을 하는 SOD의 활성을 증대시켜 $SO_2$가스의 피해를 경감시키는 효과가 인정되며, ascorbic acid와 sodium benzoate의 내성 증대 효과는 식물체내의 SOD나 POD 활성 증진과는 관계가 없는 것으로 판단된다.

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Salsolinol, a Tetrahydroisoquinoline Catechol Neurotoxin, Induces Human Cu,Zn-superoxidie Dismutase Modificaiton

  • Kang, Jung-Hoon
    • BMB Reports
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    • 제40권5호
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    • pp.684-689
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    • 2007
  • The endogenous neurotoxin, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), has been considered a potential causative factor for the pathogenesis of Parkinson's disease (PD). In the present study, we examined the pattern of human Cu,Zn-superoxide dismutase (SOD) modification elicited by salsolinol. When Cu,Zn-SOD was incubated with salsolinol, some protein fragmentation and some higher molecular weight aggregates were occurred. Salsolinol led to inactivation of Cu,Zn-SOD in a concentration-dependent manner. Free radical scavengers and catalase inhibited the salsolinol-mediated Cu,Zn-SOD modificaiton. Exposure of Cu,Zn-SOD to salsolinol led also to the generation of protein carbonyl compounds. The deoxyribose assay showed that hydroxyl radicals were generated during the oxidation of salsolinol in the presence of Cu,Zn-SOD. Therefore, the results indicate that free radical may play a role in the modification and inactivation of Cu,Zn-SOD by salsolinol.

Carnosine and Related Compounds Protect against the Hydrogen Peroxide-Mediated Cytochrome c Modification

  • Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
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    • 제27권5호
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    • pp.663-666
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    • 2006
  • Carnosine, homocarnosine and anserine might act as anti-oxidants and free radical scavengers in vivo. In the present study, the protective effects of carnosine and related compounds on the $H_2O_2$-mediated cytochrome c modification were studied. Carnosine, homocarnosine and anserine significantly inhibited the oligomerization of cytchrome c induced by $H_2O_2$. All three compounds also inhibited the formation of carbonyl compound and dityrosine during the incubation of cytochrome c with $H_2O_2$. These compounds effectively inhibited the peroxidase activity in the cytchrome c treated with $H_2O_2$. The results suggested that carnosine, homocarnosine, and anserine might protect cytochrome c against $H_2O_2$-mediated oxidative damage through a free radical scavenging.

Free Radical Toxicology and Cancer Chemoprevention

  • Lin, Jen-Kun
    • Toxicological Research
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    • 제17권
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    • pp.83-88
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    • 2001
  • Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

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