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褪黑素和槲皮素作为对抗二氧化钛纳米颗粒诱导的线粒体功能障碍的对策的作用。

Role of melatonin and quercetin as countermeasures to the mitochondrial dysfunction induced by titanium dioxide nanoparticles.

机构信息

Department of Toxicology, School of Life and Chemical Sciences, Jamia Hamdard, New Delhi 110 062, India.

Department of Biology, College of Science, Al-Zulfi-, Majmaah University, Majmaah 11952, Riyadh Region, Saudi Arabia; Health and Basic Science Research Centre, Majmaah University, Majmaah 11952, Saudi Arabia.

出版信息

Life Sci. 2023 Sep 1;328:121403. doi: 10.1016/j.lfs.2023.121403. Epub 2023 Jan 18.

DOI:10.1016/j.lfs.2023.121403
PMID:36669677
Abstract

AIM

Due to the growing commercialization of titanium dioxide nanoparticles (TNPs), it is necessary to use these particles in a manner that is safe, healthy and environmental friendly. Through reactive oxygen species (ROS) generation, it has been discovered that TNPs have a harmful effect on the brain. The aim of this study is to provide valuable insights into the possible mechanisms of TNPs induced mitochondrial dysfunction in brain and its amelioration by nutraceuticals, quercetin (QR) and melatonin (Mel) in in vitro and in vivo conditions.

MATERIALS AND METHODS

Whole brain mitochondrial sample was used for in-vitro evaluation. Pre-treatment of QR (30 μM) and Mel (100 μM) at 25 °C for 1 h was given prior to TNPs (50 μg/ml) exposure. For in-vivo study, male Wistar rats were divided into four groups. Group I was control and group II was exposed to TNPs (5 mg/kg b.wt., i.v.). QR (5 mg/kg b.wt.) and Mel (5 mg/kg b.wt.) were given orally as pre-treatment in groups III and IV, respectively. Biochemical parameters, neurobehavioural paradigms, mitochondrial respiration, neuronal architecture assessment were assessed.

KEY FINDINGS

QR and Mel restored the mitochondrial oxidative stress biomarkers in both the studies. Additionally, these nutraceuticals resuscitated the neurobehavioural alterations and restored the neuronal architecture alterations in TNPs exposed rats. The mitochondrial dysfunction induced by TNPs was also ameliorated by QR and Mel by protecting the mitochondrial complex activity and mitochondrial respiration rate.

SIGNIFICANCE

Results of the study demonstrated that QR and Mel ameliorated mitochondrial mediated neurotoxic effects induced by TNPs exposure.

摘要

目的

由于二氧化钛纳米粒子(TNPs)的商业化不断发展,因此有必要以安全、健康和环保的方式使用这些粒子。通过产生活性氧(ROS),已经发现 TNPs 对大脑有有害影响。本研究的目的是提供有关 TNPs 诱导脑线粒体功能障碍的可能机制的有价值的见解,以及在体外和体内条件下通过营养保健品槲皮素(QR)和褪黑素(Mel)对此进行改善。

材料和方法

使用全脑线粒体样本进行体外评估。在 TNPs(50μg/ml)暴露之前,将 QR(30μM)和 Mel(100μM)于 25°C 下预处理 1 小时。对于体内研究,雄性 Wistar 大鼠分为四组。第 I 组为对照组,第 II 组暴露于 TNPs(5mg/kg b.wt.,iv.)。第 III 组和第 IV 组分别给予 QR(5mg/kg b.wt.)和 Mel(5mg/kg b.wt.)作为预处理。评估了生化参数、神经行为范式、线粒体呼吸、神经元结构评估。

主要发现

QR 和 Mel 在两项研究中均恢复了线粒体氧化应激生物标志物。此外,这些营养保健品还恢复了 TNPs 暴露大鼠的神经行为改变,并恢复了神经元结构改变。QR 和 Mel 通过保护线粒体复合物活性和线粒体呼吸率,也改善了 TNPs 诱导的线粒体功能障碍。

意义

研究结果表明,QR 和 Mel 改善了 TNPs 暴露引起的线粒体介导的神经毒性作用。

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