Towards the mechanisms involved in the antioxidant action of MnIII [meso-tetrakis(4-N-methyl pyridinium) porphyrin] in mitochondria

Aerobic organisms are afforded with an antioxidant enzymatic apparatus that more recently has been recognized to include cytochrome c, as it is able to prevent hydrogen peroxide generation by returning electrons from the superoxide ion back to the respiratory chain. The present study investigated the glutathione peroxidase (GPx), superoxide dismutase (SOD) and cytochrome c-like antioxidant activities of para Mn(III)TMPyP in isolated rat liver mitochondria (RLM) and mitoplasts. In RLM, (MnTMPyP)-T-III decreased the lipid-peroxide content associated with glutathione (GSH) depletion consistent with the use of GSH as a reducing agent for high valence states of (MnTMPyP)-T-III. SOD and cytochrome c antioxidant activities were also investigated. (MnTMPyP)-T-II was able to reduce ferric cytochrome c, indicating the potential to remove a superoxide ion by returning electrons back to the respiratory chain. In antimicyn A-poisoned mitoplasts, (MnTMPyP)-T-III efficiently decreased the EPR signal of DMPO-OH adduct concomitant with GSH depletion. The present results are consistent with SOD and GPx activities for (MnTMPyP)-T-III and do not exclude cytochrome c-like activity. However, considering that para (MnTMPyP)-T-III more efficiently reduces, rather than oxidizes, superoxide ion; electron transfer from the (MnTMPyP)-T-II to the respiratory chain might not significantly contribute to the superoxide ion removal, since most of (MnTMPyP)-T-II is expected to be produced at the expense of NADPH/GSH oxidation. The present results suggest GPx-like activity to be the principal antioxidant mechanism of (MnTMPyP)-T-III, whose efficiency is dependent on the NADPH/GSH content in cells.