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N-乙酰半胱氨酸和乙酰左旋肉碱对幼鱼和成年斑马鱼急性 PTZ 诱导性惊厥的影响。

Effects of N-acetylcysteine and acetyl-L-carnitine on acute PTZ-induced seizures in larval and adult zebrafish.

机构信息

Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

出版信息

Pharmacol Rep. 2023 Dec;75(6):1544-1555. doi: 10.1007/s43440-023-00536-7. Epub 2023 Oct 9.

Abstract

BACKGROUND

Epilepsy is a prevalent neurological disease, affecting approximately 1-2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to current pharmacological treatments. Consequently, exploring alternative therapeutic options for managing this condition is crucial. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of glutamatergic neurotransmission.

METHODS

This study aimed to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances.

RESULTS

Our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and increased latencies to higher scores of epileptic seizures.

CONCLUSION

Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.

摘要

背景

癫痫是一种常见的神经系统疾病,影响全球约 1-2%的人口。癫痫的标志是癫痫发作的发生,其特征是反映疾病潜在神经机制的可预测行为变化。不幸的是,大约 30%的患者对当前的药物治疗没有反应。因此,探索管理这种疾病的替代治疗选择至关重要。两种潜在的候选药物可减轻癫痫发作,即 N-乙酰半胱氨酸 (NAC) 和乙酰左旋肉碱 (ALC),因为它们通过调节谷氨酸能神经传递显示出有希望的神经保护作用。

方法

本研究旨在评估不同浓度(0.1、1.0 和 10 mg/L)的 NAC 和 ALC 对成年和幼虫阶段斑马鱼中急性 PTZ 诱导的癫痫发作的影响。评估行为参数,如癫痫发作强度和达到危机的潜伏期,可以深入了解这些物质的疗效。

结果

我们的结果表明,这两种药物在任何测试浓度下都不能减少 PTZ 诱导的癫痫发作。另一方面,地西泮的给药显著降低了癫痫发作强度,并增加了更高分数的癫痫发作的潜伏期。

结论

因此,我们得出结论,在本研究中采用的条件下,NAC 和 ALC 对斑马鱼的急性发作没有任何显著影响。

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