Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat brain homogenates. 1994

A B Kozlov, and E A Ostrachovitch, and I B Afanas'ev
Vitamin Research Institute, Moscow, Russia.

The mechanism of the inhibitory effects of chelators (desferrioxamine, EDTA, rutin, phenanthroline and ADP) on the production of oxygen radicals in the Fenton reaction and on lipid peroxidation of rat brain homogenates has been studied. It was found that the inhibitory effects of the chelators correlated well with their abilities to oxidize ferrous ions in solution and brain homogenates. On these grounds, it was concluded that the oxidation of Fe2+ ions inside a ferrous ion-chelator complex is a major mechanism of inhibitory effects of these chelators on free radical processes. It is proposed that this mechanism is also realized during therapeutic treatment with chelators of patients with "free radical" pathologies such as Fanconi anemia, beta-thalassemia and Diamond-Blackfan anemia.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007502 Iron Chelating Agents Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems. Iron Chelates,Agents, Iron Chelating,Chelates, Iron,Chelating Agents, Iron
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D010618 Phenanthrolines Phenanthroline
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003676 Deferoxamine Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D004492 Edetic Acid A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. EDTA,Edathamil,Edetates,Ethylenediaminetetraacetic Acid,Tetracemate,Calcium Disodium Edetate,Calcium Disodium Versenate,Calcium Tetacine,Chelaton 3,Chromium EDTA,Copper EDTA,Coprin,Dicobalt EDTA,Disodium Calcitetracemate,Disodium EDTA,Disodium Ethylene Dinitrilotetraacetate,Distannous EDTA,Edetate Disodium Calcium,Edetic Acid, Calcium Salt,Edetic Acid, Calcium, Sodium Salt,Edetic Acid, Chromium Salt,Edetic Acid, Dipotassium Salt,Edetic Acid, Disodium Salt,Edetic Acid, Disodium Salt, Dihydrate,Edetic Acid, Disodium, Magnesium Salt,Edetic Acid, Disodium, Monopotassium Salt,Edetic Acid, Magnesium Salt,Edetic Acid, Monopotassium Salt,Edetic Acid, Monosodium Salt,Edetic Acid, Potassium Salt,Edetic Acid, Sodium Salt,Ethylene Dinitrilotetraacetate,Ethylenedinitrilotetraacetic Acid,Gallium EDTA,Magnesium Disodium EDTA,N,N'-1,2-Ethanediylbis(N-(carboxymethyl)glycine),Potassium EDTA,Stannous EDTA,Versenate,Versene,Acid, Edetic,Acid, Ethylenediaminetetraacetic,Acid, Ethylenedinitrilotetraacetic,Calcitetracemate, Disodium,Dinitrilotetraacetate, Disodium Ethylene,Dinitrilotetraacetate, Ethylene,Disodium Versenate, Calcium,EDTA, Chromium,EDTA, Copper,EDTA, Dicobalt,EDTA, Disodium,EDTA, Distannous,EDTA, Gallium,EDTA, Magnesium Disodium,EDTA, Potassium,EDTA, Stannous,Edetate, Calcium Disodium,Ethylene Dinitrilotetraacetate, Disodium,Tetacine, Calcium,Versenate, Calcium Disodium
D004578 Electron Spin Resonance Spectroscopy A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING. ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical

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