研究赭曲霉毒素 A 诱导人类星形胶质细胞细胞毒性的机制以及 N-乙酰半胱氨酸的保护作用。

IF 2.7 4区 医学 Q3 TOXICOLOGY Journal of Applied Toxicology Pub Date : 2024-05-29 DOI:10.1002/jat.4652
Che-Sheng Chu, Ying-Tso Chen, Wei-Zhe Liang
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引用次数: 0

摘要

赭曲霉毒素 A(OTA)是一种霉菌毒素,常见于生食和加工食品中。我们必须了解这种毒素,因为如果大量食用它,会损害人体健康。OTA 可在各种细胞模型中诱发毒性效应。然而,我们需要更全面地了解 OTA 对人类星形胶质细胞的有害影响。本研究评估了 OTA 对 Gibco® 人类星形胶质细胞(GHA)细胞系的神经毒性效应、其潜在机制以及抗氧化剂 N-乙酰半胱氨酸(NAC)的预防能力。暴露于 5-30 μM 的 OTA 会诱发浓度依赖性细胞毒性。在经 OTA 处理的细胞中,活性氧(ROS)水平明显升高,而谷胱甘肽(GSH)含量则显著下降。对 OTA 处理过的细胞进行的 Western 印迹分析显示,Bax、裂解的 caspase-9/caspase-3 蛋白水平升高,Bax/Bcl-2 比率升高。此外,暴露于 OTA 会诱导与 Nrf2、HO-1 和 NQO1 蛋白表达相关的抗氧化反应。另一方面,NAC 的预处理部分缓解了 OTA 的显著毒性作用。总之,我们的研究结果表明,氧化应激和细胞凋亡参与了 OTA 诱导的 GHA 细胞毒性。NAC 可作为一种保护剂,防止 OTA 诱导的氧化损伤。
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Investigation of the mechanisms behind ochratoxin A-induced cytotoxicity in human astrocytes and the protective effects of N-acetylcysteine

Ochratoxin A (OTA) is a type of mycotoxin commonly found in raw and processed foods. It is essential to be aware of this toxin, as it can harm your health if consumed in high quantities. OTA can induce toxic effects in various cell models. However, a more comprehensive understanding of the harmful effects of OTA on human astrocytes is required. This study evaluated OTA's neurotoxic effects on the Gibco® Human Astrocyte (GHA) cell line, its underlying mechanisms, and the antioxidant N-acetylcysteine (NAC) ability to prevent them. OTA exposure within 5–30 μM has induced concentration-dependent cytotoxicity. In the OTA-treated cells, the levels of reactive oxygen species (ROS) were found to be significantly increased, while the glutathione (GSH) contents were found to decrease considerably. The western blotting of OTA-treated cells has revealed increased Bax, cleaved caspase-9/caspase-3 protein levels, and increased Bax/Bcl-2 ratio. In addition, exposure to OTA has resulted in the induction of antioxidant responses associated with the protein expressions of Nrf2, HO-1, and NQO1. On the other hand, the pretreatment with NAC has partially alleviated the significant toxic effects of OTA. In conclusion, our findings suggest that oxidative stress and apoptosis are involved in the OTA-induced cytotoxicity in GHA cells. NAC could act as a protective agent against OTA-induced oxidative damage.

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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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