Amelioration of Glutamate-induced Toxicity by a New Thyrotropin-releasing Hormone (TRH) Analogue PYR-l-(2,5-Dibromo)-His-l-ProNH2.

IF 2.4 Q4 NEUROSCIENCES Annals of Neurosciences Pub Date : 2025-03-13 DOI:10.1177/09727531241305505
Mallikarjuna R Sunkara, Jitendra N Singh, C L Meena, A B Pant, Rahul Jain, Shyam S Sharma
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Abstract

Background: Glutamate has been implicated in the pathophysiology of central nervous system diseases, including stroke.

Purpose: In this study, the neuroprotective potential of the newly synthesised thyrotropin-releasing hormone (TRH) analogue [Pyr-l-(2,5-dibromo)-His-l-ProNH2; NP-2376] against glutamate-induced injury model were investigated.

Methods: Cortical neurons isolated from neonatal rats were used to evaluate the effects of the NP-2376. Cortical neurons were pre-treated with NP-2376 (6, 12 and 24 h) prior to glutamate (15 mM) exposure. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assay, and oxidative stress by chloromethyl-2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione assays.

Results: NP-2376 protected against glutamate-induced cortical neuron death and oxidative stress in a dose-dependent manner.

Conclusions: This study demonstrates the neuroprotective potential of TRH analogue NP-2376 against glutamate-induced toxicity, which is attributed to a decrease in oxidative stress.

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一种新的促甲状腺激素释放激素(TRH)类似物PYR-l-(2,5-二溴)-His-l-ProNH2可改善谷氨酸诱导的毒性。
背景:谷氨酸参与中枢神经系统疾病的病理生理,包括中风。目的:在本研究中,新合成的促甲状腺激素释放激素(TRH)类似物[pyr - 1 -(2,5-二溴)- his -l- pronh2;NP-2376]对谷氨酸损伤模型的影响。方法:采用新生大鼠皮质神经元,观察NP-2376的作用。在谷氨酸暴露(15 mM)之前,用NP-2376预处理皮质神经元(6、12和24小时)。采用3-(4,5-二甲基噻唑-2-酰基)-2,5-二苯基溴化四唑(MTT)和中性红色摄取(NRU)法测定细胞活力,采用氯甲基-2,7-二氯二氢荧光素双乙酸酯(DCFH-DA)和谷胱甘肽法测定氧化应激。结果:NP-2376对谷氨酸诱导的皮质神经元死亡和氧化应激具有剂量依赖性。结论:本研究表明TRH类似物NP-2376具有抗谷氨酸诱导毒性的神经保护作用,其机制可能与降低氧化应激有关。
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来源期刊
Annals of Neurosciences
Annals of Neurosciences NEUROSCIENCES-
CiteScore
2.40
自引率
0.00%
发文量
39
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