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Oxidative stress and mitochondrial dysfunction in brain of vinclozolin exposed animals
Neurochemistry international ( IF 4.2 ) Pub Date : 2024-02-09 , DOI: 10.1016/j.neuint.2024.105681
Livia Interdonato , Ylenia Marino , Ramona D'Amico , Daniela Impellizzeri , Marika Cordaro , Rosalba Siracusa , Enrico Gugliandolo , Gianluca Antonio Franco , Roberta Fusco , Salvatore Cuzzocrea , Rosanna Di Paola

Vinclozolin (VCZ) is a widely used fungicide in agriculture, especially in fruits and wine. Various studies have detailed the effects of VCZ exposure on different organs, but no information is available on its effects on brain tissues. This paper investigated the effects of VCZ exposure on the oxidative stress and mitochondrial dysfunction in brain tissue. C57BL/6 mice were exposed to VCZ (100 mg/kg) by oral gavage for 28 days. Mitochondrial homeostasis, often known as mitochondrial quality control, involves a range of processes, including mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy and autophagy. VCZ administration modified the mRNA expression levels of Sirt1, Sirt3, PGC-1α, TFAM, Nrf1, VDAC-1 and Cyt in brain tissue, as compared to control animals (CTR). The analyses also showed increased oxidative stress, in particular VCZ administration reduced SOD and CAT activities and GSH levels while increased T-AOC levels and lipid peroxidation. Additionally, brain tissues from VCZ group showed DNA oxidation (increased PARP-1 immunostaining) and apoptosis (increased TUNEL cells, increased expression of Bax mRNA level and reduced Bcl-2 levels). Western blot and immunohistochemical analyses showed increased mitophagic pathway with the accumulation of PINK1 and Parkin in mitochondria. Additionally, autophagic pathway was also increased with the increased expression and colocalization of LC3 with Neun and GFAP. Overall, this study showed that chronic VCZ exposure impaired mitochondrial homeostasis and increased oxidative stress in brain tissues.

中文翻译:

乙烯菌核利暴露动物大脑中的氧化应激和线粒体功能障碍

乙烯菌唑啉 (VCZ) 是一种在农业中广泛使用的杀菌剂,特别是在水果和葡萄酒中。各种研究详细介绍了 VCZ 暴露对不同器官的影响,但没有关于其对脑组织影响的信息。本文研究了 VCZ 暴露对脑组织氧化应激和线粒体功能障碍的影响。 C57BL/6 小鼠通过口服管饲法暴露于 VCZ (100 mg/kg) 28 天。线粒体稳态,通常称为线粒体质量控制,涉及一系列过程,包括线粒体生物发生、线粒体融合和裂变、线粒体自噬和自噬。与对照动物 (CTR) 相比,VCZ 给药改变了脑组织中 Sirt1、Sirt3、PGC-1α、TFAM、Nrf1、VDAC-1 和 Cyt 的 mRNA 表达水平。分析还显示氧化应激增加,特别是 VCZ 给药降低了 SOD 和 CAT 活性以及 GSH 水平,同时增加了 T-AOC 水平和脂质过氧化。此外,VCZ组的脑组织表现出DNA氧化(PARP-1免疫染色增加)和细胞凋亡(TUNEL细胞增加,Bax mRNA表达增加和Bcl-2水平减少)。 Western blot 和免疫组织化学分析显示,随着 PINK1 和 Parkin 在线粒体中的积累,线粒体自噬途径增加。此外,随着 LC3 表达的增加以及 LC3 与 Neun 和 GFAP 共定位的增加,自噬途径也增加。总体而言,这项研究表明,长期接触 VCZ 会损害线粒体稳态并增加脑组织的氧化应激。
更新日期:2024-02-09
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