Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090, Lublin, Poland.
Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090, Lublin, Poland.
Behav Brain Res. 2021 May 7;405:113185. doi: 10.1016/j.bbr.2021.113185. Epub 2021 Feb 19.
Chronic or recurrent stress is associated with reactive oxygen species (ROS) overproduction and can lead to oxidative damage, which plays important roles in neurodegenerative diseases. Mito - TEMPO is an antioxidant targeted at mitochondria. The aim of the presented study was to assess antidepressant and antioxidant efficacy of Mito - TEMPO administered alone or with fluoxetine in mice exposed to chronic stress. The evaluation of the antidepressant-like activity was based on forced swimming test (FST) and tail suspension test (TST). In order to evaluate the antioxidant potential, the level of mRNA expression of Adora1, Ogg1, Msra, Nrf2 and Tfam in the hippocampus of mice was determined. Behavioural research data showed the antidepressant effect of fluoxetine and Mito - TEMPO administered to mice alone and in combination. The molecular research results indicate a significant impact of chronic stress on the oxidation-reduction balance and an antioxidant effect of Mito - TEMPO. The results obtained in the study suggest that Mito - TEMPO protects DNA against oxidative damage and may be beneficial in the way of cellular function improvement under the conditions of chronic stress. Adora1, Msra, Nrf2 and Tfam genes may be involved in mediating the antioxidant effect of the combined treatment with fluoxetine and Mito - TEMPO.
慢性或复发性应激与活性氧(ROS)的过度产生有关,并可能导致氧化损伤,这在神经退行性疾病中起着重要作用。Mito-TEMPO 是一种针对线粒体的抗氧化剂。本研究的目的是评估单独给予 Mito-TEMPO 或与氟西汀联合给予 Mito-TEMPO 对慢性应激小鼠的抗抑郁和抗氧化作用。抗抑郁样活性的评估基于强迫游泳试验(FST)和悬尾试验(TST)。为了评估抗氧化潜力,测定了小鼠海马中 Adora1、Ogg1、Msra、Nrf2 和 Tfam 的 mRNA 表达水平。行为研究数据表明,氟西汀和 Mito-TEMPO 单独和联合给药对小鼠具有抗抑郁作用。分子研究结果表明,慢性应激对氧化还原平衡有显著影响,Mito-TEMPO 具有抗氧化作用。研究结果表明,Mito-TEMPO 可保护 DNA 免受氧化损伤,并可能在慢性应激条件下通过改善细胞功能有益。Adora1、Msra、Nrf2 和 Tfam 基因可能参与介导氟西汀和 Mito-TEMPO 联合治疗的抗氧化作用。