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金属有机骨架-199 亚急性暴露对大鼠脑组织认知功能和氧化应激水平的影响。

Effect of sub-acute exposure of metal-organic framework-199 on cognitive function and oxidative stress level of brain tissue in rat.

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

出版信息

Food Chem Toxicol. 2024 Sep;191:114866. doi: 10.1016/j.fct.2024.114866. Epub 2024 Jul 14.

Abstract

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators' expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1β were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.

摘要

金属有机骨架-199(MOF-199)是金属有机骨架的一个亚组,用于药物输送等多个医学领域。本研究旨在探究亚急性暴露于 MOF-199 对空间记忆、工作记忆、脑组织中炎症介质表达和氧化应激水平的影响。32 只雄性 Wistar 大鼠随机分为四组:对照组、MOF-199 低剂量组(0.3mg/kg)、中剂量组(3mg/kg)和高剂量组(6mg/kg)。通过尾静脉在 14 天内注射四次相关干预剂后,采用 Y 迷宫和 Morris 水迷宫(MWM)测试评估行为参数。通过铁还原抗氧化能力(FRAP)和硫代巴比妥酸反应物质(TBARS)试验测量氧化应激。采用实时荧光定量 RT-PCR(qRT-PCR)评估 TNF-α和 IL-1β的表达水平。结果显示,MOF-199 处理大鼠的工作记忆和空间学习记忆没有显著差异。此外,MOF-199 处理大鼠脑组织的氧化应激水平和炎症基因表达没有显著改变。尽管亚急性暴露于 MOF-199 没有显著的毒性作用,但为了将该物质用于与神经系统相关疾病的药物输送系统,仍需进行更多具有更长给药时间的研究。

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