title: Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins.
abstract: A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous flavin-dependent oxidoreductases. Inhibition of lipid peroxidation activities of these novel cationic porphyrins was compared using rat brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and ascorbate was used as initiators of lipid peroxidation, and two indices of lipid peroxidation (thiobarbituric acid reactive species (TBARS) and F(2)-isoprostanes) were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested were potent inhibitors of lipid peroxidation with IC(50) ranging from 0.1 to 34 microM with a metal-dependent potency of Mn(III)>>Co(III)>Zn(II). A flavin-dependent oxidoreductase antioxidant process was supported by the ability of the diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins stimulate NADPH oxidation in rat brain homogenates. These data suggest that metalloporphyrins may have differential antioxidant effects in tissues due to the presence or absence of flavin-dependent oxidoreductases.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA.
authors.forename: Remy
authors.initials: R
authors.lastname: Kachadourian
authors.forename: Chris A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Elysia
authors.initials: E
authors.lastname: Min
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Day
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005415:Flavins / Q000378:metabolism*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008345:Manganese / Q000737:chemistry; D008665:Metalloporphyrins / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005415:Flavins; D008665:Metalloporphyrins; D017392:Thiobarbituric Acid Reactive Substances; D008345:Manganese; D002374:Catalase; D013482:Superoxide Dismutase