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喹啉酸对大鼠纹状体行为、形态和炎症/氧化状态表达的影响:辅酶 Q 是一种良好的保护剂吗?

Effect of Quinolinic Acid on Behavior, Morphology, and Expression of Inflammatory/oxidative Status in Rats' Striatum: Is Coenzyme Q a Good Protector?

机构信息

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil.

Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil.

出版信息

Neurotox Res. 2023 Dec;41(6):559-570. doi: 10.1007/s12640-023-00656-1. Epub 2023 Jul 29.

Abstract

Quinolinic acid (QUIN) is a toxic compound with pro-oxidant, pro-inflammatory, and pro-apoptotic actions found at high levels in the central nervous system (CNS) in several pathological conditions. Due to the toxicity of QUIN, it is important to evaluate strategies to protect against the damage caused by this metabolite in the brain. In this context, coenzyme Q (CoQ) is a provitamin present in the mitochondria with a protective role in cells through several mechanisms of action. Based on these, the present study was aimed at evaluating the possible neuroprotective role of CoQ against damage caused by QUIN in the striatum of young Wistar rats. Twenty-one-day-old rats underwent a 10-day pretreatment with CoQ or saline (control) intraperitoneal injections and on the 30th day of life received QUIN intrastriatal or saline (control) administration. The animals were submitted to behavior tests or euthanized, and the striatum was dissected to neurochemical studies. Results showed that CoQ was able to prevent behavioral changes (the open field, object recognition, and pole test tasks) and neurochemical parameters (alteration in the gene expression of IL-1β, IL-6, SOD, and GPx, as well as in the immunocontent of cytoplasmic Nrf2 and nuclear p-Nf-κβ) caused by QUIN. These findings demonstrate the promising therapeutic effects of CoQ against QUIN toxicity.

摘要

喹啉酸(QUIN)是一种具有促氧化剂、促炎和促凋亡作用的有毒化合物,在几种病理条件下中枢神经系统(CNS)中高水平存在。由于 QUIN 的毒性,评估保护大脑免受这种代谢物损伤的策略非常重要。在这种情况下,辅酶 Q(CoQ)是一种存在于线粒体中的维生素前体,通过几种作用机制在细胞中具有保护作用。基于这些,本研究旨在评估 CoQ 对年轻 Wistar 大鼠纹状体中 QUIN 损伤的可能神经保护作用。21 天大的大鼠接受 CoQ 或生理盐水(对照)腹膜内注射 10 天预处理,在生命的第 30 天接受 QUIN 纹状体内或生理盐水(对照)给药。动物接受行为测试或安乐死,纹状体被解剖进行神经化学研究。结果表明,CoQ 能够预防行为变化(旷场、物体识别和棒测试任务)和神经化学参数(IL-1β、IL-6、SOD 和 GPx 的基因表达改变,以及细胞质 Nrf2 和核 p-Nf-κβ的免疫含量)由 QUIN 引起的。这些发现表明 CoQ 对 QUIN 毒性具有有希望的治疗效果。

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