• Journal of Life Science
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• v.6 no.1
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• pp.48-55
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• 1996

Oxygen free radicals are highly reactive molecules with unpaired electrons, which are produced with in aerobic cells in the course of normal metabolic events. Normally, aerobic cells are protected from the damage of free radicals by antioxidative enzymes such as superoxide dismutase (SOD), catalase, glutathione (GSH) peroxidase, GSH S-transferase and GSH reductase which scabvenge free radicals as well as nonenzymatic antioxidants such as ceruloplasmin, albumin and nontioxidants in order to elucidate antioxidative mechanisms of red ginseng. The treatment with total saponin of red ginseng significantly devreased the contents of malondialdehyde and total free radicals in the liver. On the other hand, total saponin of red ginseng significantly increased the activities of SOD, catalase and GSH reductase and nonprotein-SH level. These results suggest that total saponin of red ginseng exerts an antioxidative effect by increasing endogenous antioxidants.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.34-48
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• 1985

In vitro effects of nitrofurantoin, an antimicrobial agent for acute and chronic urinary tract infection, on the lung microsomal lipid peroxidation and the generation of reactive oxygen radicals were investigated to elucidate the biochemical mechanisms of its in vivopulmonary toxicity. The interaction of nitrofurantoin with porcine lung microsome resulted in significant lipid peroxidation. In addition, nitrofurantoin stimulated the generation of reactive oxygen radicals, $O^{-}_{2}{\cdot},\;H_2O_2$ as well as a highly reactive secondary oxygen species, $OH{\cdot}$. The stimulation of lipid peroxidation was inhibited not only by superoxide dismutase and catalase, but also by hydroxyl radical scavengers, mannitol and thiourea. Neither singlet oxygen $({^1}O_{2})$ was detected during the incubation of microsome with nitrofurantoin, nor lipid peroxidation was inhibited by singlet oxygen scavengers. When incubated anaerobically under the nitrogen atmosphere, the ability of nitrofurantoin to stimulatle lipid peroxidation was abolished. It appears that NADPH-dependent metaboliam of nitrofurantoin in pulmonary microsome under aerobic condition is accompanied by the stimulation of lipid peroxidation through the mediation of reactive oxygen radicals, particularly hydroxyl radical. It is strongly suggested from these results that the stimulation of pulmonary microsomal lipid peroxidation by the reactive oxygen radical may be a in vivo mechanism of pulmonary toxicity caused by nitrofurantoin.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.135-145
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• 1998

Bupleury radix has been used for the treatment of fever, liver disease, inflammation in traditional medicine. The present study was carried out to evaluate the antioxidant effects of Bupleury radix aqua-acupuncture solution (BRAS) in vitro. Oxygen derived free radicals produced in the course of normal aerobic life, such as superoxide anion radical($O_2^-$ ), hydroxyl radicaI( OH), hydrogen peroxide($H_2O_2$) and singlet oxygen($^1O_2$) can attack polyunsaturated fatty acid in cell membranes, enzymes, other cell compounds, and give rise to lipid peroxidation, DNA damage, lipofuscin accumulation, structure alteration of cell membrane and cell death. In this study, antioxidant effects of BRAS on lipid peroxidation were determined according to the method of TBA. BRAS inhibited markedly peroxidation of linoleic acid during the autoxidation, and also inhibited lipid peroxidation induced by hydroxyl radical derived from $H_2O_2-Fe^{2+}$ in rat liver homogenate. And BRAS showed 30% scavenging effect on DPPH radical, also exhibited a 30% inhibitory effect on superoxide generation from xanthine-xanthine oxidase system. In addition, BRAS protected the cell death induced by tert-butyl hydroperoxide(t-BHP) and significantly increased cell viability in the normal rat liver cell(Ac2F).

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.25-31
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• 2002

This study was carried out to identify the effect of oxidative stress on the pathogenesis of manganese intoxication. Five rats in experimental group were given with $MnCl_2$intraperitoneally for 4 weeks(4 mg/kg once daily 5 days per week) and another five rats for control group were given with normal saline. In experimental group, manganese concentrations increased significantly in nucleus accumbens by 142% (p<0.05), SOD activities increased significantly by 124%(p<0.01), and MDA concentrations increased significantly 148%(p<0.05) compared with control group. Among fatty acids, total n-6 polyunsaturated fatty acids(PU) increased significantly by 231%(p<0.05) compared with control group. Arachidonic acids(AA) increased by 224%(p<0.05), and these increase were composed mostly of n-6 polyunsaturated fatty acids(PUFA). Among n-3 PUFAs except linolenic acids, eicosapentanolc acid(EPA) decreased significantly by 38%(p 0.01) and docosahexanoic acids(DHA) decreased by 30% p<0.05) compared with control group. Our results suggest that the oxygen free radicals produced by manganese may cause compositional changes of fBtty acids in nucleus accumbens of the rat. Characteristics of fatty acids compositional changes by manganese were the decrease of EPAs and DHAs(n-3 PUFAs), and increase of AAs(n-6 PUFAs). These changes with the increase of MDA, suggest that manganese neurotokxcity is caused by lipid perokidation mediated with oxygen free radicals, especially superoxide radicals.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.79-89
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• 1985

Mechanism of calcium transport inhibition of cardiac sarcoplasmic reticulum (SR) by oxygen free radicals was examined. Effects of oxygen free radicals generated by xanthine/xanthine oxidase (X/XO) system on isolated porcine ventricle SR were studied with respect to its calcium binding, lipid peroxidation, SH-group content and alteration of membrane protein components. The results are as follows. 1) Calcium binding of isolated SR was markedly inhibited by X/XO. 2) During the incubation of sarcoplasmic reticulum with xanthine/xanthine oxidase, there were marked inclose in lipid peroxidation and reduction of SH-group content. 3) An antioxidant, p-phenylenediamine effectively prevented the lipid peroxidation but partially prevented the calcium binding inhibition of X/XO treated SR. 4) The reduction of SH-group content of SR treated with X/XO was partially prevented by p-phenylendiamine. 5) When modifying SH-group of SR by treatment with DTNB, the inhibition of calcium binding activity was partially prevented. 6) On gel-permeation chromatography of X/XO-treated sarcoplasmic reticulum, there was an increase of small molecular weight products, probably protein degradation products. 7) Semicarbazide, which prevents the cross-linking reaction of protein components, did not affect the calcium binding inhibition of X/XO-treated SR. From these results, it is suggested that the inhibition of calcium binding of SR by oxygen free radicals results from the consequence of multiple changes of SR components, which are lipid peroxidation, SH-group oxidation and degradation of protein components.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.319-327
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• 1994

Background: The pathogenetic mechanism of adult respiratory distress syndrome(ARDS) is not clearly defined yet, but it is well known that increased pulmonary capillary permeabilty is characteristic feature of ARDS. The increased alveolar-capillary permeability is usually preceded by damage of pulmonary artery endothelial cells. The released enzymes and oxygen free radicals from the activated neutrophils seem to play a predominant role in endothelial cell cytotoxicity. The activated neutrophils, however, probably are not the sole contributing factor in this type of damage because many cases of ARDS have been reported in severe neutropenia. Bacterial endotoxin perse and/or oxygen free radicals released from endothelial cells are suggested to be possible factors that contribute to the development of ARDS. The purpose of this study is to investigate the direct cytotoxicity of endotoxin and the role of oxygen free radicals released from the endothelial cells in endotoxin-induced endothelial cell cytotoxicity. Methods: First, to investigate whether endotoxin is cytotoxic to HUVE by itself, various doses of endotoxin were added to culture medium and cytotoxicity was measured. Second, to evaluate the possible role of oxygen free radical in endotoxin-induced HUVE cytotoxicity, various antioxidants were added on the endotoxin-induced HUVE cytotoxicity and cytotoxicity was measured. Third, to verify the release of oxygen free radicals from HUVE, the concentrations of hydrogen peroxide in the endotoxin-treated culture supernatant were measured. Finally, to observe the cytotoxic effect of hydrogen peroxide, HUVE cytotoxicity in the presence of various doses of hydrogen peroxide was measured. The fourth generations of subcultured HUVE from primary culture were used. The cell cytotoxicity was quantified by the chromium-51 release assay. Results: 1) Endotoxin alone showed HUVE cytotoxicity in a dose-dependent fashion. 2) Endotoxin-induced HUVE cytotoxicity was significantly attenuated by the pretreatment of catalase and DMTU. 3) Hydrogen peroxide was released from HUVE after endotoxin treatment in a dose-dependent fashion. 4) Exogenous hydrogen peroxide also showed HUVE cytotoxicity in a dose-dependent fashion. Conclusion: These results suggest that endotoxin alone can directly injure HUVE, and, oxygen-free radicals released from HUVE in response to endotoxin may also participate in the endotoxin-induced HUVE cytotoxicity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.89-89
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• 2002

It is well known that oxygen radicals induce neuronal cell damage by initiation of lipid peroxidation chain reaction. Recent work has been also demonstrated that enzymatically generated free radicals cause the release of glutamate and aspartate from cultured rat hippocampal slices.(omitted)

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.313-322
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• 1995

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

• Environmental Analysis Health and Toxicology
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• v.8 no.3_4
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• pp.23-32
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• 1993

This study was designed to elucidate the mechanism of nephrotoxicity caused by antitumor agent tetraphosphine platinum (II) complex (RC-1), which was synthesized as a tetraphosphine Pt (II) derivatives recently. Rats treated with RC-1 (20mg/kg/day) showed the increase of BUN value and malondialdehyde contents in kidney homogenate, compared to the control and which means the lipid peroxidation was a main cause of nephrotoxicity. In order to investigate the cytotoxic mechanism of RC-1, we also tested and revealed the generation of oxygen free radicals derived from neutrophil stimulated by RC-1 and interaction of the oxygen free radicals with the erythrocyte membrane. From the above results, we suggest that nephrotoxicity of general platinum (II) antitumor compounds as well as RC-1 were inhibited by radical scavengers.

• Korean Journal of Plant Resources
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• v.23 no.3
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• pp.207-213
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• 2010

Hovenia dulcis Thunb fruits were successively extracted with hot water, water, methanol, ethyl acetate, and chloroform. The crude extracts were investigated for potential antioxidant by measuring scavenging against DPPH free radicals, reducing power, superoxide radicals, and protection of protein damage and cultured cells from a lethal dose of hydrogen peroxide ($H_2O_2$). In all chemical assays used, the hot water extract of H. dulcis fruits, which contained $61.14{\pm}2.57$ (Tannic acid mg/g extract, n=3) of total phenolic compounds contents exhibited highest activity in in vitro models of DPPH free radical scavenging activity, reducing power assay, superoxide radical scavenging activity and protection of protein damage. In addition, the hot water extract protected cultured RAW 264.7 macrophages from a lethal dose of $H_2O_2$ and reduced reactive oxygen species level in RAW 264.7 cells.