Free radical research communications最新文献

{"title":"Inhibition of the iron-catalysed formation of hydroxyl radicals by nitrosouracil derivatives: protection of mitochondrial membranes against lipid peroxidation.","authors":"A Rabion,&nbsp;J B Verlhac,&nbsp;L Fraisse,&nbsp;B Roche,&nbsp;J L Seris","doi":"10.3109/10715769309056530","DOIUrl":"https://doi.org/10.3109/10715769309056530","url":null,"abstract":"<p><p>A new series of metal ligands containing the 1,3-dimethyl-6-amino-5- nitrosouracil moiety has been synthesized and they have been studied as potential inhibitors of iron-dependent lipid peroxidation. For this purpose, these new derivatives have been tested in the Fenton induced deoxyribose degradation assay, which allows a quantitative measurement of their inhibitory effect towards hydroxyl radical generation. When iron(II) is complexed by these ligands, a strong inhibition of deoxyribose degradation is observed, especially in the case of tris-[2-(1,3-dimethyl-5-nitrosouracil-6-yl)aminoethyl] amine (5). This inhibitory effect is clearly related to a specific complexation of iron(II) and is not due to the direct scavenging of hydroxyl radical by the ligand. Inhibition of the iron mediated Fenton reaction presumably results from inactivation of the reactivity of the metal center towards hydrogen peroxide. These derivatives, as well as long alkyl chain substituted nitrosouracils were evaluated in the protection of biological membranes against lipid peroxidation (induced by iron(II)/dihydroxyfumaric acid and determined with the 2-thiobarbituric acid test). Ligand 5 inhibited lipid peroxidation at a rate similar to Desferal (desferrioxamine B) and slightly higher than bathophenanthroline sulphonate (BPS), which are respectively good iron(III) and iron(II) chelators. When covalently bound with a long alkyl chain, the increase of lipophilic character of the ligand allows its location near the mitochondrial membrane, where lipid peroxidation occurs. Lower concentrations (IC50 = 4 microM) are then necessary to inhibit lipid peroxidation. This IC50 concentration should be compared to those obtained for Trolox (IC50 = 3 microM) or the 21-aminosteroid U74500A (IC50 = 1 microM) described previously.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 6","pages":"409-23"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19159586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosinase-induced phenoxyl radicals of etoposide (VP-16): interaction with reductants in model systems, K562 leukemic cell and nuclear homogenates.","authors":"D Stoyanovsky,&nbsp;J Yalowich,&nbsp;T Gantchev,&nbsp;V Kagan","doi":"10.3109/10715769309056527","DOIUrl":"https://doi.org/10.3109/10715769309056527","url":null,"abstract":"<p><p>Etoposide (VP-16) is an antitumor drug currently in use for the treatment of a number of human cancers. Mechanisms of VP-16 cytotoxicity involve DNA breakage secondary to inhibition of DNA topoisomerase II and/or direct drug-induced DNA strand cleavage. The VP-16 molecule contains a hindered phenolic group which is crucial for its antitumor activity because its oxidation yields reactive metabolites (quinones) capable of irreversible binding to macromolecular targets. VP-16 phenoxyl radical is an essential intermediate in VP-16 oxidative activation and can be either converted to oxidation products or reduced by intracellular reductants to its initial phenolic form. In the present paper we demonstrate that the tyrosinase-induced VP-16 phenoxyl radical could be reduced by ascorbate, glutathione (GSH) and dihydrolipoic acid. These reductants caused a transient disappearance of a characteristic VP-16 phenoxyl radical ESR signal which reappeared after depletion of the reductant. The reductants completely prevented VP-16 oxidation by tyrosinase during the lag-period as measured by high performance liquid chromatography; after the lag-period VP-16 oxidation proceeded with the rate observed in the absence of reductants. In homogenates of human K562 leukemic cells, the tyrosinase-induced VP-16 phenoxyl radical ESR signal could be observed only after a lag-period whose duration was dependent on cell concentration; VP-16 oxidation proceeded in cell homogenates after this lag-period. In homogenates of isolated nuclei, the VP-16 phenoxyl radical and VP-16 oxidation were also detected after a lag-period, which was significantly shorter than that observed for an equivalent amount of cells. In both cell homogenates and in nuclear homogenates, the duration of the lag period could be increased by exogenously added reductants. The duration of the lag-period for the appearance of the VP-16 phenoxyl radical signal in the ESR spectrum can be used as a convenient measure of cellular reductive capacity. Interaction of the VP-16 phenoxyl radical with intracellular reductants may be critical for its metabolic activation and cytotoxic effects.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 6","pages":"371-86"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19159583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPR spin trapping of free radicals produced by bleomycin and ascorbate.","authors":"G R Buettner,&nbsp;P L Moseley","doi":"10.3109/10715769309056s89","DOIUrl":"https://doi.org/10.3109/10715769309056s89","url":null,"abstract":"<p><p>In the presence of ascorbate, bleomycin (BLM) is converted to a redox-inactive form that is incapable of inducing DNA strand scission. We have employed EPR spin trapping with 5,5-dimethylpyrroline-1-oxide (DMPO) to examine free radical production during this process. The introduction of ascorbate to an Fe(III)BLM-DMPO system results in the formation of three EPR observable free radicals. One of these radicals is the resonance-stabilized ascorbate free radical (aH = 1.8 G) that is not spin trapped by DMPO; the other two are the result of DMPO spin trapping. These radicals appear to be two carbon-centered radicals, DMPO/.CR1, (aN1 = 15.75 G, aH1 = 22.30 G, aN/aH = 0.706) and DMPO/.CR2 (aN2 = 15.20 G, aH2 = 19.20 G, aN/aH = 0.79). Although it is not possible to identify the exact structures of the carbon-centered radicals that are spin trapped, the hyperfine splittings, as well as the aN/aH values, are characteristic of the presence of electron-withdrawing groups, such as the oxygen atom when attached to the carbon atom. In fact, these parameters are characteristic of DMPO spin trapping results obtained when sugars are subjected to oxidative insult from HO.. Thus, these BLM-ascorbate produced radicals may well be derived from the sugar moiety of BLM.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S89-93"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056s89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18514824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of heme proteins by vitamin E, selenium, and beta-carotene against oxidative damage in rat heart, kidney, lung and spleen.","authors":"H Chen,&nbsp;A L Tappel","doi":"10.3109/10715769309111601","DOIUrl":"https://doi.org/10.3109/10715769309111601","url":null,"abstract":"<p><p>Effects of the combination of vitamin E, selenium, and beta-carotene on oxidative damage to rat heart, kidney, lung, and spleen were studied by measurement of the production of oxidized heme proteins (OHP) during spontaneous and prooxidant-induced oxidation. Male SD rats were fed with a vitamin E and selenium deficient diet or a diet supplemented with vitamin E, selenium, and beta-carotene. Homogenates of heart, kidney, lung, and spleen were incubated at 37 degrees C with and without the presence of bromotrichloromethane (CBrCl3). The diet supplemented with antioxidants showed a strong protective effect against oxidative damage to heme proteins during the early stages of both spontaneous and CBrCl3-induced oxidation in contrast to the antioxidant deficient diet. Synergism of multiple antioxygenic nutrients against oxidative damage to various animal tissues is discussed.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 3","pages":"183-90"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309111601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19233905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in plasma antioxidant status during eccentric exercise and the effect of vitamin supplementation.","authors":"S R Maxwell,&nbsp;P Jakeman,&nbsp;H Thomason,&nbsp;C Leguen,&nbsp;G H Thorpe","doi":"10.3109/10715769309111602","DOIUrl":"https://doi.org/10.3109/10715769309111602","url":null,"abstract":"<p><p>Twenty-four healthy students undertook one hour of box-stepping exercise. Prior to exercise eight had received no medication (Group A), eight received 400 mg of vitamin C daily for three weeks before and one week after exercise (Group C) and eight received 400 mg of vitamin E for the same period (Group E). Groups C and E had significantly higher levels of vitamin C (p < 0.01) and vitamin E (p < 0.01) respectively than group A at the commencement of exercise. Plasma total antioxidant capacity rose significantly during exercise in all group (A - p < 0.05; C - p < 0.001; E - p < 0.001). This rise was accounted for by increases in plasma uric acid in all groups. In addition there were significant increases in vitamin C in group C (p < 0.001) and vitamin E in group E (p < 0.05). There were no significant changes in plasma malondialdehyde following exercise in any group. It is concluded that plasma antioxidant capacity rises in response to one hour of eccentric exercise and that the contribution of individual antioxidants to this change can be influenced by vitamin supplementation. The possible mechanisms of the antioxidant changes during exercise and their implications are discussed.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 3","pages":"191-202"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309111602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19233906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radical trapping by PBN during reperfusion in rabbit gastric mucosa.","authors":"M Sonoda,&nbsp;G Asakuno,&nbsp;M Matsuki,&nbsp;A Satomi,&nbsp;K Ishida,&nbsp;Y Sakagishi","doi":"10.3109/10715769309056s185","DOIUrl":"https://doi.org/10.3109/10715769309056s185","url":null,"abstract":"<p><p>Oxygen free radicals have been considered as a cause of ischemia-reperfusion injury in several organs, but this injury in a stomach, containing acid, may progress to severe damage. Thus, we examined the effect of ischemia-reperfusion and milk-intake on rabbit gastric mucosa. The gastric mucosal blood flow was increased after milk-intake, and gastric rupture was detected. Superoxide dismutase activity measured by an improved nitroblue tetrazolium reduction method and thiobarbituric acid reactive substances in serum is increased during ischemia-reperfusion and milk-intake. By using alpha-phenyl N-tert-butyl nitrone (PBN) as a spin trap and electron paramagnetic resonance (EPR), we detected lipidic radicals from tissue samples in chloroform-methanol solvent only during reperfusion and milk-intake period; no signal was detected before. The EPR signal of spin adducts obtained in the sample after ischemia-reperfusion and milk-intake would be a mixture of peroxyl and alkoxyl radicals from the analysis of coupling constants.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S185-91"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056s185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19269696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo EPR measurement of radical reaction in whole mice--influence of inspired oxygen and ischemia-reperfusion injury on nitroxide reduction.","authors":"H Utsumi,&nbsp;K Takeshita,&nbsp;Y Miura,&nbsp;S Masuda,&nbsp;A Hamada","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In vivo EPR measurements were carried out with whole mice to evaluate the influence of inspired oxygen and ischemia-reperfusion injury on spin-clearance of the nitroxide radicals which were administered intravenously or intramuscularly. Nitroxide radicals in head, abdomen, or muscle domains were composed of sharp triplet lines. The peak heights decreased gradually with time. The reduction of nitroxide radicals depended both on the inspired oxygen concentration and on the domains. Femoral ischemia-reperfusion injury also affected spin-clearance of the nitroxide radical in the thigh. The results were discussed with regard to the generation of active oxygen species.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S219-25"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19269700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant properties of antiulcer Kampo medicines.","authors":"S Takahashi,&nbsp;T Yoshikawa,&nbsp;Y Naito,&nbsp;Y Minamiyama,&nbsp;T Tanigawa,&nbsp;M Kondo","doi":"10.3109/10715769309056s101","DOIUrl":"https://doi.org/10.3109/10715769309056s101","url":null,"abstract":"<p><p>Kampo medicines, aqueous extracts of a mixture of natural crude drugs, have numerous ingredients. Recent pharmacologic studies on Kampo medicines have clarified their many and varied biological activities. In this study, based on recent research that has been directed toward the excellent antioxidant properties of Kampo medicines, we investigated antioxidant activities of three Kampo medicines (TJ-10, TJ-35, TJ-43), which are clinically used for gastritis or peptic ulcer, by the electron paramagnetic resonance (EPR) spin trapping method. These Kampo medicines, especially TJ-35 scavenged superoxide generated from the hypoxanthine-xanthine oxidase system, and slightly inhibited the superoxide generation from polymorphonuclear leukocytes stimulated by phorbol myristate acetate or opsonized zymosan. Three Kampo medicines, especially TJ-35 also inhibited the generation of hydroxyl radicals by the Fenton reaction. These results suggest that these antioxidant properties may be partly responsible for anti-ulcer actions of these three Kampo medicines, especially TJ-35.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S101-8"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056s101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19270499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tert-butylhydroperoxide bioactivation to methyl radical in rat liver mitochondria and submitochondrial particles.","authors":"A Iannone,&nbsp;A Bini,&nbsp;Y G Jin,&nbsp;V Vannini,&nbsp;A Tomasi","doi":"10.3109/10715769309056s141","DOIUrl":"https://doi.org/10.3109/10715769309056s141","url":null,"abstract":"<p><p>Electron paramagnetic resonance spectroscopy (EPR) coupled to the spin trapping technique was used to detect carbon-centered radicals in rat liver mitochondria and submitochondrial particles exposed to t-butyl-hydroperoxide (TBH), using the spin trapping agent 3,5-dibromo-4-nitroso-benzenesulfonic acid (DBNBS). The signal recorded was unambiguously assigned to the methyl radical adduct. DBNBS was added to isolated rat liver mitochondria energized with succinate, and the methyl radical adduct was observed. The addition of NADH, NADPH, inhibitors of the respiratory chain, and of monoaminoxidase (MAO) inhibitors did not cause any relevant modification in the yield of radical adduct formation. Boiling and the addition of a non-ionic detergent inhibited the formation of the radical adduct, while experiments carried out under hypoxic conditions generated a significant increase in methyl radical formation. Further experiments were carried out on sub-mitochondrial particles (SMP) giving rise to, basically, the same results. From the above results, we are proposing that haem prosthetic groups are the likely source of TBH bioactivation in mitochondria.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S141-7"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056s141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19271054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Force field calculations on five membered ring aminoxyl radicals.","authors":"F Vila,&nbsp;P Tordo,&nbsp;D Siri,&nbsp;G Pèpe","doi":"10.3109/10715769309056s17","DOIUrl":"https://doi.org/10.3109/10715769309056s17","url":null,"abstract":"<p><p>Two force fields (MM2 and Genmol) have been applied to the modeling of five membered ring aminoxyl radicals. For the six molecules which were investigated the geometry of the conformation with the lowest strain energy was in very good agreement with the X-ray geometry. However owing to the high flexibility of five membered rings other conformations were shown to have a strain energy close to the energy minimum.</p>","PeriodicalId":12438,"journal":{"name":"Free radical research communications","volume":"19 Suppl 1 ","pages":"S17-22"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10715769309056s17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19271058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}