MnTBAP Chloride

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Background

Superoxide (O(2)(·-)) is the proximal mitochondrial reactive oxygen species underlying pathology and redox signaling. This central role prioritizes development of a mitochondria-targeted reagent selective for controlling O(2)(·-). MnTBAP is a novel, stable and cell-permeable superoxide dismutase mimetic. In vitro: Due to its superoxide dismutase mimetic property, 50 microM MnTBAP was found to attenuate the injury produced dose-dependently by exposure to various concentrations of paraquat for 4 h. MnTBAP also protected endothelial cells in a dose-dependent manner against paraquat. The protective effect of MnTBAP appears to be caused by its intracellular superoxide-scavenging activity because neither the zinc form nor CuZnSOD protected the cells against paraquat-induced injury [1]. In vivo: Local administration of MnTBAP significantly and reduced carrageenan-induced paw oedema dose-dependently at all time points, which was related to its superoxide dismutase mimetic property. MnTBAP also caused a significant dose-dependent reduction in paw myeloperoxidase activity, as well as preventing histological injury. Immunohistochemical analyses for nitrotyrosine showed a positive staining in paw from carrageenan-treated rats [2]. Clinical trial: Up to now, MnTBAP is still in the preclinical development stage.

[1] Day BJ, Shawen S, Liochev SI, Crapo JD. A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury, in vitro. J Pharmacol Exp Ther. 1995 Dec;275(3):1227-32.
[2] Cuzzocrea S, Costantino G, Mazzon E, Zingarelli B, De Sarro A, Caputi AP. Protective effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in paw oedema induced by carrageenan in the rat. Biochem Pharmacol. 1999 Jul 1;58(1):171-6.