title: 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.
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Xinwei
authors.initials: X
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Shenglong
authors.initials: S
authors.lastname: Xu
authors.forename: XiaoLi
authors.initials: X
authors.lastname: Sun
authors.forename: YuKun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000162:Acoustics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007858:Learning; D008297:Male; D008568:Memory; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D009589:Nitrogen Oxides; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; C039900:nitroxyl