title: Opposite effects of Mn(III) and Fe(III) forms of meso-tetrakis(4-N-methyl pyridiniumyl) porphyrins on isolated rat liver mitochondria.
abstract: The relevance of porphyrins as therapeutic drugs targeted to mitochondria has been widely recognized. In this work, we studied the action of meso-tetrakis porphyrins (TMPyP) on respiring rat liver mitochondria. Mn(III)TMPyP exerted a protective effect against lipid peroxidation induced by Fe(II) or the azo initiator 4,4'-azobis(4-cyanopentanoic acid) (ABCPA), which partition in the hydrophobic phospholipid moiety, and 2,2'-azobis(2-amidinepropane)dihydrochloride (ABAP), which partitions in the aqueous phase. In contrast, Fe(III)TMPyP itself induced an intense lipid peroxidation, accompanied by mitochondrial permeability transition. Both mesoporphyrins studied promoted a release of mitochondrial state-4 respiration, in the concentration range of 1.0-20 microM. Based on the relative effects of Mn(III)TMPyP against ABAP and ABCPA-induced lipid peroxidation, we believe that meso-tetrakis porphyrins must concentrate preferably at membrane-water interfaces.
authors.affiliation: Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Nepomuceno
authors.forename: M
authors.initials: M
authors.lastname: Tabak
authors.forename: A E
authors.initials: AE
authors.lastname: Vercesi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000187:drug effects; D007501:Iron / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008665:Metalloporphyrins; D011166:Porphyrins; C092399:meso-tetrakis(1-methyl-4-pyridiniumyl)porphyrin; D008345:Manganese; D007501:Iron