The effects of Mn(III) ortho N-alkylpyridyl- and diortho N,N’- imidazolylporphyrins on Oxygen and Glucose Deprivation- Induced Cell Death in Mixed Neuronal/Glial Cortical Cell Cultures

In vivo investigations have confirmed the beneficial effects of hydrophilic, cationic Mn(III)-based catalytic antioxidants in models of oxidative stress. We hypothesized the octyl porphyrin, MnTnOct-2-PyP5+, a lipophilic but equally potent antioxidant, would be more efficacious in reducing oxygen and glucose deprivation (OGD)-induced cell death. Using a cell culture model of rat mixed neuronal/glial cells, we investigated the effect of MnTnOct-2-PyP5+ on the OGD-induced cell death as compared to the effects of widely studied hydrophilic analogues MnTE-2-PyP5+ and MnTDE-2-ImP5+ P and a standard compound, dizocilpine (MK-801). Cell death was evaluated at 24 hours using lactate dehydrogenase (LDH) release, 3-(4,5-dimethyltiazol-2-yl)-2,5 diphenyltetrazolium bromide(MTT) and propidium iodide staining. At lower concentrations, all three porphyrins reduced cell death as compared to cultures exposed to OGD alone. When the cultures were exposed to MnTnOct-2-PyP5+ before OGD but not during the deprivation, it was a very efficacious compound as judged by LDH release. MnTnOct-2-PyP5+ becomes less efficacious if the exposure was prolonged. While no extensive toxicity was seen with MnTnOct-2-PyP5+ P, the effects observed, though, might have been the result of the interplay of efficacy and toxicity leading to a diminished protectiveness