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Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.

Publication ,  Journal Article
Celic, T; Španjol, J; Bobinac, M; Tovmasyan, A; Vukelic, I; Reboucas, JS; Batinic-Haberle, I; Bobinac, D
Published in: Free Radic Res
December 2014

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.

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Published In

Free Radic Res

DOI

EISSN

1029-2470

Publication Date

December 2014

Volume

48

Issue

12

Start / End Page

1426 / 1442

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Spinal Cord Ischemia
  • Reperfusion Injury
  • Rats, Sprague-Dawley
  • Rats
  • Oxidative Stress
  • NF-kappa B
  • Metalloporphyrins
  • Manganese
  • Female
 

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Celic, T., Španjol, J., Bobinac, M., Tovmasyan, A., Vukelic, I., Reboucas, J. S., … Bobinac, D. (2014). Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways. Free Radic Res, 48(12), 1426–1442. https://doi.org/10.3109/10715762.2014.960865
Celic, T., J. Španjol, M. Bobinac, A. Tovmasyan, I. Vukelic, J. S. Reboucas, I. Batinic-Haberle, and D. Bobinac. “Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.Free Radic Res 48, no. 12 (December 2014): 1426–42. https://doi.org/10.3109/10715762.2014.960865.
Celic T, Španjol J, Bobinac M, Tovmasyan A, Vukelic I, Reboucas JS, et al. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways. Free Radic Res. 2014 Dec;48(12):1426–42.
Celic, T., et al. “Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.Free Radic Res, vol. 48, no. 12, Dec. 2014, pp. 1426–42. Pubmed, doi:10.3109/10715762.2014.960865.
Celic T, Španjol J, Bobinac M, Tovmasyan A, Vukelic I, Reboucas JS, Batinic-Haberle I, Bobinac D. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways. Free Radic Res. 2014 Dec;48(12):1426–1442.

Published In

Free Radic Res

DOI

EISSN

1029-2470

Publication Date

December 2014

Volume

48

Issue

12

Start / End Page

1426 / 1442

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Spinal Cord Ischemia
  • Reperfusion Injury
  • Rats, Sprague-Dawley
  • Rats
  • Oxidative Stress
  • NF-kappa B
  • Metalloporphyrins
  • Manganese
  • Female