摘要:

The peroxidation of liposomes by a haem peroxidase and hydrogen peroxide in the presence of indole-3-acetic acid and derivatives was investigated. It was found that these compounds can accelerate the lipid peroxidation up to 65 fold and this is attributed to the formation of peroxyl radicals that may react with the lipids, possibly by hydrogen abstraction. The peroxyl radicals are formed by peroxidase-catalyzed oxidation of the enhancers to radical cations which undergo cleavage of the carbon-carbon bond on the side-chain to yield CO2 and carbon-centred radicals that rapidly add oxygen. In competition with decarboxylation, the radical cations deprotonate reversibly from the Nl position. Rates of decarboxylation,pKavalues and rate of reaction with the peroxidase compound I indicate consistent substituent effects which, however, can not be quantitatively related to the usual Hammett or Brown parameters. Assuming that the rate of decarboxylation of the radical cations taken is a measure of the electron density of the molecule (or radical), it is found that the efficiency of these compounds as enhancers of lipid peroxidation increases with increasing electron density, suggesting that, at least in the model system, the oxidation of the substrates is the limiting step in causing lipid peroxidation.

ISSN:1071-5762    

DOI:10.3109/10715769509065262

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Thein vitroantioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) was measured and the ability of BPH4 to prevent paraquat-induced cell damage was examined in cultured hepatocytes. The scavenging activity of BPH4 against superoxide anion radicals was assayed in two systems, i.e., xanthine/xanthine oxidase (X/XOD) and rat macrophage/phorbol myristate acetate (MξPMA) radical-generating systems. BPH4 showed an extremely strong superoxide anion radical-scavenging activity in both assay systems. Biopterin (BP) itself did not show any activity in the X/XOD system, but was effective in the MξPMA system. The antioxidative activities of BPH4 against both superoxide anion and hydroxyl radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected rat brain homogenate against auto-oxidation. We further examined the effect of BPH4 on paraquat-induced cell toxicity in cultured rat hepatocytes. The paraquat-induced elevation of the release of lactate dehydrogenase (LDH), a marker enzyme for cytotoxicity from cultured hepatocytes was suppressed by BPH4 in a dose-dependent manner. The elevation of lipid peroxides simultaneously induced by paraquat was also inhibited by BPH4 in the same manner. These results suggest that BPH4 might be useful in the treatment of various diseases whose pathogenesis is active oxygen-related.

ISSN:1071-5762    

DOI:10.3109/10715769509065263

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Free radicals generated by benzoyl peroxide-mediated catalytic decomposition of bromotrichloromethane (eg. trichloromethyl) were allowed to react under nitrogen or under air with uracil. Under nitrogen two reaction products were formed, one was identified as 5-chlorouracil and the other as a 5-bromouracil. Under air, besides the above two products other nine were also formed: 5,6-dihydrouracil; 5-hydroxyuracil; a chlorohydroxy adduct of uracil; a bromohydroxy derivative of uracil having the 5,6 bond in the saturated form; other bromohydroxy derivative of uracil having the double bond intact; 5,6-dihydroxyuracil; two dihalogenated hydroxylated uracil derivatives and one peak we were not able to descipher its structure. No single reaction product formed had carbon centered radicals (eg. trichloromethyl) added from CBrCl3and consequently would be missed in‘in vivo’covalent binding studies wherel4C haloalkane (CBrCl3or carbon tetrachloride) were employed. If similar reaction products resulted during interaction of CBrCl3reactive metabolites with uracil in RNAs, significant deleterious effects in their function would be expected. That possibility, however, remains to be established.

ISSN:1071-5762    

DOI:10.3109/10715769509065264

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The remarkable vasorelaxant and anti-platelet effects of FK409 have been reported to be due to nitric oxide (NO) release. The purpose of the present study is to investigate the spontaneous NO-releasing pathway of FK409 in aqueous solutions. 'H-NMR spectra of FK409 suggested that the compound underwent a time-dependent elimination of the hydrogen atom at a-position of the nitro moiety (at the 5-position) in weakly alkaline solutions. In addition, the degradation of FK409 monitored by HPLC showed a pH-dependency accelerating with an increase of pH. These results revealed that the first step in the degradation of FK409 might be the hydroxyl ion-dependent subtraction of the hydrogen atom at the 5-position. On the other hand, NO release from FK409 also exhibited a pH-dependency, and the velocity of NO liberation was markedly enhanced above pH 6. Furthermore, a linear relationship between the rate of FK409 degradation and that of NO formation was observed, indicating that the rate-limiting step for NO formation is the same as that for degradation. Thus, the rate-limiting process of NO formation from FK409 is due to the deprotonation reaction of the hydrogen atom at the 5-position by hydroxyl ions. The deprotonation process appears to be an essential step for both FK409 degradation and NO release. On the basis of the results, a possible kinetic scheme for NO release from FK409 is proposed.

ISSN:1071-5762    

DOI:10.3109/10715769509065265

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The question whether hydroxyl free radicals are formed in the reactions of divalent iron complexes Fe(II)L; L = edta; hedta; tcma (tcma = l-acetato-l,4,7-triazacyclononane) with hydrogen peroxide in neutral and slightly acidic solutions was studied by using theβelimination reaction as an assay for the formation of hydroxyl free radicals, OH. The results show that at pH<5.5 the iron(II)peroxide intermediate complex decomposes rapidly to yield free hydroxyl radicals for L=edta and hedta. This is in contrast to the mechanism of the corresponding Fe(II)nta peroxide complex, which probably decomposes to form Fe(IV)nta which then reacts with organic substrates to yield aliphatic free radicals. Thus, the non-participating ligand L has an appreciable effect on the mechanism of reaction of the metal center with hydrogen peroxide. Blank experiments using ionizing radiation as the source of CH2CR(CH3)OH, R = H or CH3radicals indicate that when L = tcma intermediates of the type LFeIII-CH2CR(CH3)OHaqare formed, but their major mode of decomposition is not theβelimination reaction. Thus, the present assay for the formation of hydroxyl free radicals by the Fenton Reaction does not fit the latter system.

ISSN:1071-5762    

DOI:10.3109/10715769509065266

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Oxidation of low density lipoproteins (LDL) in blood vessel walls plays a significant role in the development of atherosclerosis. LDL oxidationin vitrois greatly accelerated by the presence of“catalytic”iron or copper ions, which have already been shown to be present within advanced atherosclerotic lesions. We demonstrate here that mechanical damage to human arterial wall samples (both normal and early or intermediate atherosclerotic lesions) causes release of“catalytic”iron and copper ions, to an extent increasing with the damage. It may be that traumatic (e.g. during angioplasty) or other injury to the vessel wall contributes to the generation of metal ions that can facilitate LDL oxidation and other free radical reactions, so promoting atherosclerosis.

ISSN:1071-5762    

DOI:10.3109/10715769509065267

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Intracellular levels of H2O2 in BHK-21 cells are not static but decline progressively with cell growth. Exposure of cells to inhibitors of catalase, or glutathione peroxidase, not only diminishes this decline but also depresses rates of cell proliferation, suggesting important growth regulatory roles for those antioxidant enzymes. Other agents which also diminish the growth-associated decline in intracellular levels of H2O2, such as the superoxide dismutase mimic, copper II—(3,5-diisopropylsalicylate)2, or docosahexaenoic acid, also reduced cell proliferation. In contrast, proliferation can be stimulated by the addition of 1μM exogenous H2O2to the culture medium. Under these conditions, however, intracellular levels of H2O2are unaffected, whereas there is a reduction in intracellular levels of glutathione. It is argued that critical balances between intracellular levels of both H2O2and glutathione are of significance in relation both to growth stimulation and inhibition. In addition growth stimulatory concentrations of H2O2, whilst initially leading to increased intracellular levels of lipid peroxidation breakdown products, appear to“trigger”their metabolism, possibly through aldehyde dehydrogenase, whose activity is also stimulated by H2O2

ISSN:1071-5762    

DOI:10.3109/10715769509065268

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

A human supplementation study was undertaken in order to investigate the correlation between the intake of individual daily dosages of vitamin E (300 mg), vitamin C (250 mg), orβ-carotene (15 mg) of eight week duration and their uptakein vivoin plasma and LDL. The effects of a combined supplement of vitamin E, vitamin C andβ-carotene (Redoxon protector-75 mg, 150 mg, 15 mg respectively) were also investigated. The results show that on supplementation with the individual antioxidants the increases in plasmaα-tocopherolxholesterol levels lie in the 1.5-2 fold range and theβ-carotene:cholesterol ratios give a mean 3.5 fold enhancement. The combined supplement containing the same level ofβ-carotene as the single dosage achieved comparative levels of uptake in plasma. The level of plasma vitamin C appears to be maximal at about 100//M regardless of the pre-supplementation level.

ISSN:1071-5762    

DOI:10.3109/10715769509065269

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Natural Antioxidants in Human Health and Disease Edited by Balz Frei Academic Press, San DiegoIn VitroToxicology Edited by: Shayne Cox Gad Raven Press Ltd.: New York, 290pp ISBN: 0-88167-974-7Active Oxygen, Lipid Peroxidation and Antioxidants Edited by Kunio Yagi Japan Scientific Society Press: Tokyo ISBN 4-7622-6738-4, 1993 CRC Press: Boca Raton ISBN 0-8493-7769-2, 1993 x +372 pages Y 13, 000Free Radicals, Cardiovascular Dysfunction and Protection Strategies R C Kukreja and M L Hess R G Landes Company: Austin, Texas, USA, 1994Oxygen and Environmental Stress in Plants (Special issue of the Proceedings of the Royal Society of Edinburgh, volume 102 1994) eds R M M Crawford, G A F Hendry and B A GoodmanMitochondria: DNA, Proteins and Disease Eds. V. Darley Usmar and A.H.V. Schapira Portland Press Research Monograph V, London, 1994Human Medicinal Agents From Plants Edited by A. Douglas Kinghorn and Manuel F. Balandrin ACS Symposium Series 534 American Chemical Society: Washington DC, 1993, pp. xii + 356. ISBN 08412 2705 5. $89.95.

ISSN:1071-5762    

DOI:10.3109/10715769509065270

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:1071-5762    

DOI:10.3109/10715769509065271

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor