Manganic porphyrins possess catalase activity and protect endothelial cells against hydrogen peroxide-mediated injury.
Manganic porphyrins are redox active metal complexes that have been employed as superoxide dismutase mimics. We tested whether these metalloporphyrins could also dismute hydrogen peroxide (H2O2) and whether they could protect endothelial cells against H2O2. Both of the manganic metalloporphyrins tested were found to catalytically dismute H2O2. These manganic porphyrins also protected endothelial cells in dose-dependent manners against H2O2-mediated injury with MnTMPyP having an EC50 of 8 microM and MnTBAP having an EC50 of 15 microM. The zinc containing analogs of these porphyrins were inactive in dismuting H2O2 and did not protect. These studies further define the antioxidant capacity of metalloporphyrins in converting superoxide to H2O2 and H2O2 to water. These data suggest that manganic porphyrins may be useful therapeutics against disease states associated with the overproduction of reactive oxygen species.
Day
B J
BJ
Department of Biochemistry, Duke University, Durham, North Carolina 27710, USA. dayb@njc.org
Fridovich
I
I
Crapo
J D
JD
D000818:Animals; D002374:Catalase; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D008345:Manganese; D008665:Metalloporphyrins / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D008345:Manganese; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D006861:Hydrogen Peroxide; D002374:Catalase