Herein we have demonstrated that both
superoxide dismutase (SOD) mimic, cationic
Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP(3-)), protect against oxidative stress caused by
spinal cord ischemia/reperfusion via suppression of
nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the
DNA binding of NF-κB in an aqueous system, whereas MnTBAP(3-) was not. Here, for the first time, in a complex in vivo system-animal model of
spinal cord injury-a similar impact of MnTBAP(3-), at a dose identical to that of MnTnHex-2-PyP(5+), was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before
ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn
porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling
protein regulating astrocyte activation, was detected and found to correlate well with the suppression of
astrogliosis (as
glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in
glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP(3-) with
reactive nitrogen species (RNS) (.NO/HNO/ONOO(-)) suggests that RNS/
MnTBAP(3-)-driven modification of NF-κB
protein cysteines may be involved in its
therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP(5+) which presumably occurs via
reactive oxygen species and relates to NF-κB
thiol oxidation; the role of RNS cannot be excluded.