| Prooxidant activity of ferrioxamine in isolated rat hepatocytes and linoleic acid micelles. | |
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MedLine Citation:
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PMID: 10207126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The complex iron-desferrioxamine (ferrioxamine) is considered chemically unreactive, and not able to participate in redox cycle reactions. Desferrioxamine-dependent toxicity is, however, described in both human and animal studies. The aim of this work was to test the possibility that chelated iron, under certain circumstances, could enter redox reactions, giving an explanation of desferrioxamine side effects. Carefully prepared ferrioxamine, to obtain a 1:1 desferrioxamine:iron ratio, was added to isolated rat hepatocytes and to linoleic acid micelles. A strong prooxidant and cytotoxic effect was observed in the cells, also potentiating tert-butyl hydroperoxide-induced lipid peroxidation. In micelles, the prooxidant effect was observed only in the presence of ascorbate, which is oxidized during the process, giving rise to ascorbyl radical. Ferrioxamine, under the experimental conditions used, did not release iron, indicating that the prooxidant effect was due to iron redox cycling. The addition of desferrioxamine prevented both ferrioxamine- and tert-butyl hydroperoxide-induced lipid peroxidation and cytotoxicity. Concurrently, a nitroxide radical was detected, an indication of the radical scavenger activity of the hydroxamic moiety. No radical species was observed when ferrioxamine was added to the same system. The prooxidant effect of ferrioxamine gives a possible explanation of the reported human and animal desferrioxamine toxicity. When, in compartmentalized regions, the ratio of desferrioxamine:metal reaches 1:1, ferrioxamine is formed. In the absence of metal-free desferrioxamine, ferrioxamine can participate in redox cycling reactions, initiating lipid peroxidation and cytotoxicity. |
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Authors:
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S Bergamini; C Rota; M Staffieri; A Tomasi; A Iannone |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemical research in toxicology Volume: 12 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-05-11 Completed Date: 1999-05-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 365-70 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, University of Modena, 41100 Modena, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ascorbic Acid / pharmacology Deferoxamine / pharmacology* Ferric Compounds / pharmacology* Iron Chelating Agents / pharmacology* Linoleic Acid / metabolism* Lipid Peroxidation / drug effects Liver / drug effects*, metabolism Male Micelles Oxidants / pharmacology* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Ferric Compounds; 0/Iron Chelating Agents; 0/Micelles; 0/Oxidants; 14836-73-8/ferrioxamine B; 2197-37-7/Linoleic Acid; 50-81-7/Ascorbic Acid; 70-51-9/Deferoxamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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