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一氧化氮可能参与胞磷胆碱对小鼠戊四氮和电休克诱发惊厥的抗惊厥作用。

Posible involvement of nitric oxide in anticonvulsant effects of citicoline on pentylenetetrazole and electroshock induced seizures in mice.

作者信息

Rasooli Rokhsana, Pirsalami Fatema, Moezi Leila

机构信息

Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Heliyon. 2020 May 19;6(5):e03932. doi: 10.1016/j.heliyon.2020.e03932. eCollection 2020 May.

Abstract

Cerebroneurovascular trauma is recognized as an important risk factor in the development of seizure and epilepsy. Administration of citicoline in these situations is a conventional therapeutic strategy, which combines neurovascular protection and repair effects. The aim of the present study is clarifying the effect of acute and sub-chronic citicoline administration on pentylenetetrazole (PTZ) and electroshock induced seizures in mice. Besides we examined the probable role of NO and its interaction with citicoline in seizure experiments. Male mice were received acute and sub-chronic regimens of different doses of citicoline (62.5, 125, 250 and 500 mg/kg) before the intravenous or intraperitoneal PTZ-induced seizures or electroshock. To clarify the probable role of NO, 7-nitroindazole (7-NI) (60 mg/kg) or aminoguanidine (AG) (100 mg/kg) were injected 5 min before citicoline in separate groups. The results revealed that neither acute nor sub-chronic treatment with citicoline could affect the seizures induced by intravenous or intraperitoneal PTZ, but in electroshock model, citicoline showed anti-epileptic properties. Co-administration of citicoline and selective nitric oxide synthase (NOS) inhibitors amplified the anticonvulsant effect of citicoline. The current results indicated that citicoline has anticonvulsant effects probably through the inhibition of NO.

摘要

脑-神经血管损伤被认为是癫痫发作和癫痫发展的一个重要危险因素。在这些情况下给予胞磷胆碱是一种传统的治疗策略,它兼具神经血管保护和修复作用。本研究的目的是阐明急性和亚慢性给予胞磷胆碱对小鼠戊四氮(PTZ)和电休克诱导的癫痫发作的影响。此外,我们在癫痫发作实验中研究了一氧化氮(NO)的可能作用及其与胞磷胆碱的相互作用。在静脉或腹腔注射PTZ诱导的癫痫发作或电休克之前,雄性小鼠接受不同剂量(62.5、125、250和500 mg/kg)的胞磷胆碱急性和亚慢性给药方案。为了阐明NO的可能作用,在不同组中于胞磷胆碱给药前5分钟注射7-硝基吲唑(7-NI)(60 mg/kg)或氨基胍(AG)(100 mg/kg)。结果显示,无论是急性还是亚慢性给予胞磷胆碱均不能影响静脉或腹腔注射PTZ诱导的癫痫发作,但在电休克模型中,胞磷胆碱表现出抗癫痫特性。胞磷胆碱与选择性一氧化氮合酶(NOS)抑制剂联合给药增强了胞磷胆碱的抗惊厥作用。目前的结果表明,胞磷胆碱可能通过抑制NO发挥抗惊厥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc6d/7240119/e1faec1ec6e0/gr1.jpg

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