title: Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy.
abstract: Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose certain reactive oxygen species (ROS), similar to metalloporphyrins. We investigated whether Fe-, Mn-, and Ga-corroles have neuroprotective effects on neurons and correlated this with superoxide scavenging activity in vitro and in vivo. Apoptosis was induced in retinal ganglion cell-5 neuronal precursor cells by serum deprivation. Cell death was measured with sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate and calcein-AM/propidium iodide assays. Fe- and Mn-corroles, but not the non-redox-active Ga-corrole used as control, reduced RGC-5 cell death after serum deprivation. Serum deprivation caused increased levels of intracellular superoxide, detected by an increase in the fluorescence intensity of 2-hydroxyethidium, and this was blocked by Fe- and Mn-corroles, but not Ga-corrole. In vivo real-time confocal imaging of retinas after optic nerve transection assessed the superoxide production within individual rat retinal ganglion cells. Fe- and Mn-corroles, but not Ga-corrole, scavenged neuronal superoxide in vivo. Given that the neuroprotective activity of metallocorroles correlated with superoxide scavenging activity, Fe- and Mn-corroles could be candidate drugs for delaying neuronal death after axonal injury in optic neuropathies, such as glaucoma.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Akiyasu
authors.initials: A
authors.lastname: Kanamori
authors.forename: Maria-Magdalena
authors.initials: MM
authors.lastname: Catrinescu
authors.forename: Atif
authors.initials: A
authors.lastname: Mahammed
authors.forename: Zeev
authors.initials: Z
authors.lastname: Gross
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Levin
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D056831:Coordination Complexes / Q000494:pharmacology* / Q000627:therapeutic use; D016895:Culture Media, Serum-Free; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D016895:Culture Media, Serum-Free; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D013481:Superoxides
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