Synthesis of a Novel Nitronyl Nitroxide Radical and Determination of its Protective Effects Against Infrasound-Induced Injury

Abstract

Infrasound causes functional disorders and structural injury to the central nervous system. However, few anti-infrasound drugs exist, and they are inefficient. Nitronyl nitroxide radicals have been reported to be good antioxidants that act as superoxide dismutase mimics and directly react with reactive oxygen species, such as ·OH, H2O2, and O 2 (∙) -. Our previous research showed that the nitronyl nitroxide radical L-NNNBP has good protective effects against β-amyloid deposition and memory deficits in an AD rat model of APP/PS1. The objective of the present study was to find a new group of anti-infrasound drugs and determine the underlying pharmacological actions of nitronyl nitroxide radicals against infrasound-induced neuronal impairment in vivo. We synthesized a new stable nitronyl nitroxide radical, NRbt, and characterized its crystal structure. The results of the anti-oxidative damage effects of NRbt and the positive control drug tempol showed that they could significantly increase the SOD activity, CAT activity and GSH level and decrease the MDA level in rat hippocampi compared with infrasound exposure without pretreatment. Moreover, the ability of NRbt to regulate the activity or level of these biochemical markers was better than that of tempol. Our results showed that both NRbt and tempol significantly protected against the learning and memory impairments induced by infrasound exposure in a Morris water maze, but there were no significant differences in the path length or escape latency between the rats in the tempol group and the three NRbt groups (P > 0.05). In addition, the infrasound-induced neuronal apoptosis in rat hippocampi was significantly suppressed by NRbt and tempol. The results demonstrated that compared with the infrasound exposure group, the expression of Bcl-2 was up-regulated and the expressions of Bax and caspase-3 were down-regulated in rats pretreated with NRbt (40 mg/kg) or tempol (40 mg/kg). These results showed that the newly synthesized nitronyl nitroxide radical, NRbt, may be an effective anti-infrasound drug because of its capacity to inhibit the oxidative damage of free radicals induced by infrasound exposure.

Pre-Exposure to Environmental Enrichment Protects against Learning and Memory Deficits Caused by Infrasound Exposure

“…SOD can catalyze superoxide anions into oxygen and hydrogen peroxide [ 65 ], which has an important protective role against the effects of reactive oxygen species (ROS). These results agree with some previous studies [ 9 , 11 ]. In this study, we found that pre-exposure to EE was effective to block the infrasound-induced decrease in the GSH/GSSG ratio and SOD level in the hippocampus, indicating that EE pre-exposure improved the antioxidant system.…”

“…Mammalian organs' inherent vibration frequencies are just within the range of those of infrasound; therefore, infrasound can disturb normal functions of multiple organs by triggering biological resonance [ 6 , 7 ], in which the central nervous system (CNS) is the most vulnerable organ [ 8 – 10 ]. Substantial and growing evidence has revealed that exposure to infrasound can markedly impair the learning and memory ability of rats [ 9 , 11 ]. The underlying mechanisms include enhanced neuronal apoptosis, production of proinflammatory cytokines, oxidative stress, and microglial activation in the rat hippocampus [ 11 – 13 ].…”

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

“…Infrasound also can cause brain injury by accumulating ROS [18]. Most ROS, such as OH, H 2 O 2 , and O 2 -, can be produced by infrasound [50]. Lipid accumulation is associated with ROS development [51], induces the production of mitochondrial ROS according to a previous report [52], and may increase oxidative stress in Oxidative Medicine and Cellular Longevity the cell.…”

The synthesis of new functionalized 1,3,5-triazine-based stable bi- and trinitroxides of the 2,5-dihydroimidazole series

“…It is worth noting that only a limited number of paramagnetic derivatives-mainly nitroxides, nitronyl nitroxides, and phenoxyls linked with a triazine central core-have been successfully prepared. Three strategies have been implemented to introduce various radical fragments into the 2 nd , 4 th , and 6 th positions of the heterocyclic nucleus: a) nucleophilic substitution of 1-3 chlorine atoms in cyanuric chloride with alkoxy, phenoxy, or amino groups in a reaction with the corresponding paramagnetic alcohols, [25][26][27][28] phenols, 29,30 or amines 31 ; b) organometallic reactions of a radical-protected derivative of arylboronic acid or an organolithium derivative with 2,4,6-trichlorotriazine 32 ; c) initial formation of the 1,3,5-triazine nucleus by the trimerization reaction of a functionalized benzonitrile followed by transformation of the functional group into a stable radical. 33 The present report continues our research on the synthesis of functional derivatives of spirocyclic monoand oligoradicals of the azole series.…”