Bisphenol A Induces Neuronal Apoptosis and Oxidative Stress Through TRPV4 Channel Signaling Pathways: Protective Role of Alpha-Lipoic Acid.

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES

Environmental Toxicology Pub Date : 2025-05-21 DOI:10.1002/tox.24541

Ramazan Çinar,Mustafa Nazıroğlu

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引用次数: 0

Abstract

Bisphenol A (BPA), an environmental toxin, exerts adverse effects by increasing mitochondrial (mROS) and intracellular (iROS) reactive oxygen species, apoptosis, and Ca2+ influx in neurological diseases. However, antioxidants can mitigate these detrimental effects. This study aimed to investigate the protective role of antioxidant alpha-lipoic acid (ALA) against BPA-induced TRPV4 channel stimulation, oxidant, and apoptotic changes in SH-SY5Y neuronal cells. Five experimental groups were established: control, ALA, BPA, BPA + ALA, and BPA + TRPV4 antagonist (ruthenium red, RuR). BPA increased excessive Ca2+ influx and TRPV4 current density, while BPA- and TRPV4 agonist (GSK1016790A)-induced TRPV4 stimulations were downregulated following incubation with ALA and RuR. BPA-induced increases in oxidant markers (lipid peroxidation, mROS, iROS), apoptotic markers (caspase-3, -8, and -9), Zn2+, and cell death were reduced by ALA and RuR treatment. Conversely, BPA-induced reductions in cell viability, glutathione, and glutathione peroxidase levels were restored following treatment. In summary, ALA attenuated BPA-induced excess Ca2+ influx, Zn2+ accumulation, apoptosis, and oxidative neurotoxicity via TRPV4 inhibition. Therefore, ALA may offer protection against BPA-induced neuronal cell death associated with oxidative neurotoxicity.

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双酚A通过TRPV4通道信号通路诱导神经元凋亡和氧化应激：α -硫辛酸的保护作用

双酚A （BPA）是一种环境毒素，通过增加线粒体（mROS）和细胞内（iROS）活性氧、细胞凋亡和Ca2+内流在神经系统疾病中产生不利影响。然而，抗氧化剂可以减轻这些有害影响。本研究旨在探讨抗氧化剂α -硫辛酸（ALA）对bpa诱导的SH-SY5Y神经元细胞TRPV4通道刺激、氧化和凋亡变化的保护作用。设5个实验组：对照组、ALA、BPA、BPA + ALA和BPA + TRPV4拮抗剂（RuR）。BPA增加了过量的Ca2+内流和TRPV4电流密度，而BPA-和TRPV4激动剂（GSK1016790A）诱导的TRPV4刺激在ALA和RuR孵育后下调。ALA和RuR处理可降低bpa诱导的氧化标记物（脂质过氧化、mROS、iROS）、凋亡标记物（caspase-3、-8和-9）、Zn2+和细胞死亡的增加。相反，bpa诱导的细胞活力、谷胱甘肽和谷胱甘肽过氧化物酶水平的降低在治疗后恢复。综上所述，ALA通过抑制TRPV4减弱bpa诱导的过量Ca2+内流、Zn2+积累、细胞凋亡和氧化性神经毒性。因此，ALA可能对bpa诱导的与氧化性神经毒性相关的神经元细胞死亡提供保护。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

8.90%

发文量

261

审稿时长

4.5 months

期刊介绍： The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.