Opposite effects of Mn(III) and Fe(III) forms of meso-tetrakis(4-N-methyl pyridiniumyl) porphyrins on isolated rat liver mitochondria.
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.
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Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
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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
D008665:Metalloporphyrins; D011166:Porphyrins; C092399:meso-tetrakis(1-methyl-4-pyridiniumyl)porphyrin; D008345:Manganese; D007501:Iron