Manganese complexes and the generation and scavenging of hydroxyl free radicals.
In a wide variety of biological systems non-enzyme complexes of the metals copper (Cu) and iron (Fe) have been shown to enhance oxygen radical damage by increasing the production of an oxidative species generally believed to be the hydroxyl free radical (.OH) via "Fenton" and possibly "Haber-Weiss" type reactions. However, the behavior of the chemically and biologically similar transition metal manganese (Mn) with .OH is unknown. Unlike Fe and Cu, inorganic complexes of Mn are known to exist in high concentrations in certain cells. Three different oxygen free radical generating systems and four .OH detection methods were used to investigate the activity of biologically relevant inorganic Mn complexes. These complexes were compared to compounds reported to scavenge and generate .OH. The direct and indirect effects of Mn on the .OH flux were compared by attempting to distinguish the effects of hydrogen peroxide (H2O2), superoxide (O2-), and .OH through the use of selective scavengers and generators. Mn-EDTA and biologically relevant Mn-pyrophosphates and polyphosphates, in contrast to Fe-EDTA, do not generate .OH in these systems. The results suggest that Mn in various forms does, indeed, inhibit oxy-radical damage mediated by .OH, but only if the .OH production is dependent on the presence of O2- or H2O2. Thus, with .OH, as with O2- and H2O2, Mn complexes appear to behave in a fundamentally different fashion from Cu and Fe.
Cheton
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PL
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Archibald
F S
FS
D001205:Ascorbic Acid / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004249:DNA Damage; D004269:DNA, Bacterial; D011756:Diphosphates / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005030:Ethylenes / Q000096:biosynthesis; D005290:Ferric Compounds / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007501:Iron / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D017616:Magnesium Compounds; D008345:Manganese / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D010957:Plasmids; D011122:Polyphosphates / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D004269:DNA, Bacterial; D011756:Diphosphates; D005030:Ethylenes; D005290:Ferric Compounds; D005609:Free Radicals; D006878:Hydroxides; D017616:Magnesium Compounds; D011122:Polyphosphates; D013481:Superoxides; D017665:Hydroxyl Radical; D008353:Mannitol; D008345:Manganese; C014632:2-keto-4-methylthiobutyric acid; D004492:Edetic Acid; D008715:Methionine; C034732:magnesium pyrophosphate; D006861:Hydrogen Peroxide; D007501:Iron; D014969:Xanthine Oxidase; D008274:Magnesium; C019179:Fe(III)-EDTA; D001205:Ascorbic Acid