title: Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.
abstract: It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A., México D.F. 14269, México.
authors.forename: Carolina
authors.initials: C
authors.lastname: González-Cortés
authors.forename: Citlaltepetl
authors.initials: C
authors.lastname: Salinas-Lara
authors.forename: Marcos Artemio
authors.initials: MA
authors.lastname: Gómez-López
authors.forename: Martha Lilia
authors.initials: ML
authors.lastname: Tena-Suck
authors.forename: Verónica
authors.initials: V
authors.lastname: Pérez-De La Cruz
authors.forename: Daniel
authors.initials: D
authors.lastname: Rembao-Bojórquez
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.forename: Celedonio
authors.initials: C
authors.lastname: Gómez-Ruiz
authors.forename: Sonia
authors.initials: S
authors.lastname: Galván-Arzate
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011166:Porphyrins / Q000008:administration & dosage*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D018696:Neuroprotective Agents; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate; D052247:Nitric Oxide Synthase Type II; D017378:Quinolinic Acid