1400 W, a selective inducible nitric oxide synthase inhibitor, mitigates early neuroinflammation and nitrooxidative stress in diisopropylfluorophosphate-induced short-term neurotoxicity rat model.
1400 W, a selective inducible nitric oxide synthase inhibitor, mitigates early neuroinflammation and nitrooxidative stress in diisopropylfluorophosphate-induced short-term neurotoxicity rat model.
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DOI：
10.3389/fnmol.2023.1125934
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发表时间：
2023
影响因子：
4.8
通讯作者：
Thippeswamy, Thimmasettappa
中科院分区：
文献类型：
--
作者：
Massey, Nyzil;Vasanthi, Suraj Sundara;Samidurai, Manikandan;Gage, Meghan;Rao, Nikhil;Meyer, Christina;Thippeswamy, Thimmasettappa
关键词：
有机磷神经毒剂（OPNA）暴露可诱导急性和长期神经功能缺损。亚致死浓度的OPNA暴露诱导乙酰胆碱酯酶和胆碱能毒性蛋白的不可逆抑制，并发展癫痫持续状态（SE）。持续性癫痫发作与ROS/RNS产生增加、神经炎症和神经变性相关。共1400 W是一种新型小分子，它不可逆地抑制诱导型一氧化氮合酶（iNOS），并已被证明能有效减少ROS/RNS的产生。在这项研究中，我们研究了1400 W治疗一周或两周，每天10 mg/kg或15 mg/kg的大鼠二异丙基氟磷酸盐（DFP）模型的影响。与溶媒相比，1400 W显著减少了脑不同区域中小胶质细胞、星形胶质细胞和NeuN+FJB阳性细胞的数量。1400 W还显著降低血清中的硝基氧化应激标志物和促炎细胞因子。然而，两种浓度的1400 W治疗2周对混合性别队列（雄性或雌性）治疗期间的癫痫样峰频率和自发性癫痫发作均无任何显著影响。DFP暴露或1400 W处理的反应没有显着的性别差异。总之，1400 W以15 mg/kg/天治疗两周在显著降低DFP诱导的硝基氧化应激、神经炎症和神经退行性变化方面更有效。
Organophosphate nerve agent (OPNA) exposure induces acute and long-term neurological deficits. OPNA exposure at sub-lethal concentrations induces irreversible inhibition of acetylcholinesterase and cholinergic toxidrome and develops status epilepticus (SE). Persistent seizures have been associated with increased production of ROS/RNS, neuroinflammation, and neurodegeneration. A total of 1400W is a novel small molecule, which irreversibly inhibits inducible nitric oxide synthase (iNOS) and has been shown to effectively reduce ROS/RNS generation. In this study, we investigated the effects of 1400W treatment for a week or two weeks at 10 mg/kg or 15 mg/kg per day in the rat diisopropylfluorophosphate (DFP) model. 1400W significantly reduced the number of microglia, astroglia, and NeuN+FJB positive cells compared to the vehicle in different regions of the brain. 1400W also significantly reduced nitrooxidative stress markers and proinflammatory cytokines in the serum. However, neither of the two concentrations of 1400W for two weeks of treatment had any significant effect on epileptiform spike rate and spontaneous seizures during the treatment period in mixed sex cohorts, males, or females. No significant sex differences were found in response to DFP exposure or 1400W treatment. In conclusion, 1400W treatment at 15 mg/kg per day for two weeks was more effective in significantly reducing DFP-induced nitrooxidative stress, neuroinflammatory and neurodegenerative changes.
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DOI：
10.1111/febs.15428
发表时间：
2020-11
期刊：
The FEBS journal
影响因子：
--
作者：
Bosco DB;Tian DS;Wu LJ
通讯作者：
Wu LJ
影响因子：
3.4
作者：
Chapman, Shira;Yaakov, Guy;Grauer, Ettie
通讯作者：
Grauer, Ettie
DOI：
10.1016/j.bbadis.2017.02.003
发表时间：
2017-06
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Clossen BL;Reddy DS
通讯作者：
Reddy DS
影响因子：
5.6
作者：
Cardenas-Rodriguez N;Huerta-Gertrudis B;Rivera-Espinosa L;Montesinos-Correa H;Bandala C;Carmona-Aparicio L;Coballase-Urrutia E
通讯作者：
Coballase-Urrutia E
影响因子：
11.4
作者：
Cobley JN;Fiorello ML;Bailey DM
通讯作者：
Bailey DM