papa-nonoate and oxyhyponitrite

Nitric oxide, (·)NO, and product of its one-electron reduction, nitroxyl NO(-), are important molecules in the biochemistry of living organisms. At physiological conditions nitroxyl exists in its protonated form, HNO. Angeli's salt, AS, and diazeniumdiolates, NONOates, are widely used donors of HNO and (·)NO, correspondingly. In this work we observed oxidative decomposition of AS and PAPA NONOate in the presence of mild oxidizing agents, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, cPTIO, and 2,2'-azinobis(3-ethylbenzolthiazoline-6-sulfonate) radical, ABTS(·-). The observed unexpected fast oxidative decomposition of AS with release of NO instead of HNO suggests the need for a reevaluation of some of the biological effects of AS assigned to action of HNO. While oxidative decomposition of NONOate did not result in release of alternative NOx specimen but only (·)NO, it significantly affects the rates and stoichiometry of (·)NO release. In summary, possible contribution of oxidative decomposition of AS and NONOates should be taken into account upon interpretation of their actions in chemical and biological systems.

Topics: Hydrazines; Molecular Structure; Nitric Oxide; Nitrites; Oxidation-Reduction

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.. 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.

Topics: Animals; Dizocilpine Maleate; Hydrazines; Injections, Spinal; Male; Motor Activity; Motor Neurons; Nitric Oxide; Nitric Oxide Donors; Nitrites; Nitrogen Oxides; Nitrous Oxide; Rats; Rats, Wistar; Spinal Cord; Time Factors