Competing approaches to excitotoxic neuroprotection by inert and catalytic antioxidant porphyrins

Neuroscience Letters
Joseph S TauskelaPaul Morley

Abstract

The goal of this study was to determine if novel porphyrins protect cultured cortical neurons from excitotoxic NMDA exposure or oxygen-glucose deprivation (OGD), which model key aspects of cerebral ischemia. Porphyrins were chosen based on conventional and unconventional criteria. Metalloporphyrin catalytic antioxidants possessing a redox-sensitive metal core can exhibit potent and wide-ranging catalytic antioxidant abilities, which are conventionally believed to underlie neuroprotection. We report here that a recent-generation potent peroxynitrite decomposition catalyst, FP-15, protected a majority of neurons against OGD and NMDA toxicity, without suppressing NMDA-mediated intracellular Ca2+ (Cai2+) elevations or whole-cell currents. We have previously shown that neuroprotection against OGD and NMDA toxicity correlated with an ability to suppress neurotoxic Cai2+ elevations and not antioxidant ability. We now evaluate if this unconventional mechanism extends to inert metal-free porphyrins. Neuron cultures were completely protected against OGD and NMDA toxicity by H2-meso-tetrakis(3-benzoic acid)porphyrin (H2-TBAP(3)) or H2-meso-tetrakis(4-sulfonatophenyl)porphyrin (H2-TPPS(4)), although only H2-TPPS(4) suppressed (completely) ...Continue Reading

References

Aug 27, 1999·Trends in Pharmacological Sciences·M Patel, B J Day
Oct 4, 2002·Free Radical Biology & Medicine·Huaxin ShengDavid S Warner
Jun 20, 2003·American Journal of Physiology. Cell Physiology·Joseph S TauskelaPaul Morley
Oct 3, 2003·British Journal of Pharmacology·Carolina MuscoliDaniela Salvemini
Jun 16, 2004·British Journal of Pharmacology·Meenakshisundaram ThiyagarajanShyam Sundar Sharma
Jun 19, 2004·Drug Discovery Today·Brian J Day
Jun 30, 2004·Free Radical Biology & Medicine·Ayako Okado-MatsumotoIrwin Fridovich
Jul 15, 2004·Dalton Transactions : an International Journal of Inorganic Chemistry·Ines Batinić-HaberleIrwin Fridovich
Dec 22, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Irina G ObrosovaCsaba Szabó
Feb 11, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Brian J Day, Chirag Kariya
Aug 6, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joseph S TauskelaPaul Morley

❮ Previous
Next ❯

Citations

Sep 22, 2009·Neuroscience Letters·Joseph S Tauskela, Eric Brunette
Jan 13, 2015·Expert Opinion on Therapeutic Patents·Lauren M Slosky, Todd W Vanderah
Jun 29, 2017·Brain Research Bulletin·Kristina RamdialAlvaro G Estevez
Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.