Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins |
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Authors: | Kachadourian Remy Johnson Chris A Min Elysia Spasojevic Ivan Day Brian J |
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Affiliation: | Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA. |
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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. |
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Keywords: | AEOL 10113 or MnTE-2-PyP5+, manganese(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin AEOL 10123 or MnTDM-1,3-IP5+, manganese(III) meso-tetrakis(N,N′-dimethylimidazolium-2-yl)porphyrin AEOL 10150 or MnTDE-1,3-IP5+, manganese(III) meso-tetrakis(N,N′-diethylimidazolium-2-yl)porphyrin AEOL 10158 or MnTDP-1,3-IP5+, manganese(III) meso-tetrakis(N,N′-dipropylimidazolium-2-yl)porphyrin BHT, butylated hydroxytoluene CoTDM-1,3-IP5+, cobalt(III) meso-tetrakis(N,N′-dimethylimidazolium-2-yl)porphyrin DPI, diphenyleneiodonium chloride EDTA, ethylenediaminetetraacetic acid EUK-8, manganese(III) salen F2-IP, F2-isoprostanes 2-HE, 2-hydroxyestradiol ILP, inhibition of lipid peroxidation 2-ME, 2-methoxyestradiol MDA, malondialdehyde MnTBAP, manganese(III) meso-tetrakis(4-carboxy-phenyl)porphyrin NHE, normal hydrogen electrode SOD, superoxide dismutase TBARS, thiobarbituric acid reactive species ZnTDM-1,3-IP5+, zinc(II) meso-tetrakis(N,N′-dimethylimidazolium-2-yl)porphyrin |
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