title: Angeli's salt and spinal motor neuron injury.
abstract: Nitroxyl anion or its conjugate acid (NO-/HNO) and nitric oxide (NO) may both have pro-oxidative and cytotoxic properties. Superoxide dismutase (SOD) enzyme has been shown to convert reversibly HNO to NO. Mutations found in the SOD enzyme in some familial amyotrophic lateral sclerosis (ALS) patients affect redox properties of the SOD enzyme in a manner, which may affect the equilibrium between NO and HNO. Therefore, we studied the effects of HNO releasing compound, Angeli's salt (AS), on both motor and sensory functions after intrathecal administration in the lumbar spinal cord of a male rat. These functions were measured by rotarod, spontaneous activity, paw- and tail-flick tests. In addition, we compared the effect of AS to NO releasing papanonoate, old AS solution and sulphononoate in the motor performance test. The effect of intrathecal delivery of AS on the markers of the spinal cord injury and oxidative/nitrosative stress were further studied.
  
  
  RESULTS
  Freshly prepared AS (5 or 10 micromol), but not papanonoate, caused a marked decrease in the rotarod performance 3-7 days after the intrathecal administration. The peak motor deficiency was noted 3 days after AS (5 micromol) delivery. Old, degraded, AS solution and nitrous oxide releasing sulphononoate did not decrease motor performance in the rotarod test. AS did not affect the sensory stimulus evoked responses as measured by the paw-flick and tail-flick tests. Immunohistological examination revealed that AS caused injury related changes in the expression of glial fibrillary acidic protein (GFAP), fibroblast growth factor (FGF-2) and laminins in the spinal cord. Moreover, AS increased nitrotyrosine immunoreactivity in the spinal motor neurons. Therefore, we conclude that AS, but not NO releasing papanonoate, causes motor neuron injury but does not affect the function of sensory nerves in behavioural tests.
authors.affiliation: Institute of Biomedicine (Pharmacology), Biomedicum Helsinki, P.O. Box 63, University of Helsinki 00014, Helsinki, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Väänänen
authors.forename: Ron
authors.initials: R
authors.lastname: Liebkind
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.forename: Paivi
authors.initials: P
authors.lastname: Liesi
authors.forename: Pekka
authors.initials: P
authors.lastname: Rauhala
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009573:Nitrites / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000378:metabolism; D009609:Nitrous Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D006834:Hydrazines; D020030:Nitric Oxide Donors; D009573:Nitrites; D009589:Nitrogen Oxides; C112653:PAPA NONOate; C021229:oxyhyponitrite; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D009609:Nitrous Oxide