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赭曲霉毒素A的神经毒性:分子机制与神经治疗策略

Neurotoxicity of ochratoxin A: Molecular mechanisms and neurotherapeutic strategies.

作者信息

Obafemi Blessing A, Adedara Isaac A, Rocha Joao B T

机构信息

Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil; Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.

Department of Food Science and Technology, Center of Rural Sciences, Federal University of Santa Maria, Camobi, 97105- 900 Santa Maria, RS, Brazil.

出版信息

Toxicology. 2023 Oct;497-498:153630. doi: 10.1016/j.tox.2023.153630. Epub 2023 Sep 13.

Abstract

Data from epidemiological and experimental studies have evidenced that some chemical contaminants in food elicit their harmful effects by targeting the central nervous system. Ochratoxin A is a foodborne mycotoxin produced by Aspergillus and Penicillium species. Research on neurotoxicity associated with ochratoxin A exposure has increased greatly in recent years. The present review accrued substantial evidence on the neurotoxicity associated with ochratoxin A exposure as well as discussed notable susceptible targets of noxious ochratoxin A at molecular, cellular and genetic levels. Specifically, the neurotoxic mechanisms associated with ochratoxin A exposure were unequivocally unraveled in vitro using human neuroblastoma SH-SY5Y cells, mouse hippocampal HT22 cells, human astrocyte (NHA-SV40LT) cells and microglia cells as well as in vivo using mammalian and non-mammalian models. Data from human biomonitoring studies on plasma ochratoxin A levels in patients with neurodegenerative diseases with some age- and sex-related responses were also highlighted. Moreover, the neurotherapeutic mechanisms of some naturally occurring bioactive compounds against ochratoxin A neurotoxicity are reviewed. Collectively, accumulated data from literature demonstrate that ochratoxin A is a neurotoxin with potential pathological involvement in neurological disorders. Cutting edge original translational research on the development of neurotherapeutics for neurotoxicity associated with foodborne toxicants including ochratoxin A is indispensable.

摘要

流行病学和实验研究的数据表明,食品中的一些化学污染物通过靶向中枢神经系统产生有害影响。赭曲霉毒素A是一种由曲霉属和青霉属产生的食源性霉菌毒素。近年来,与接触赭曲霉毒素A相关的神经毒性研究大幅增加。本综述积累了大量关于接触赭曲霉毒素A相关神经毒性的证据,并在分子、细胞和遗传水平上讨论了有害赭曲霉毒素A的显著易感靶点。具体而言,使用人神经母细胞瘤SH-SY5Y细胞、小鼠海马HT22细胞、人星形胶质细胞(NHA-SV40LT)和小胶质细胞在体外以及使用哺乳动物和非哺乳动物模型在体内明确揭示了与接触赭曲霉毒素A相关的神经毒性机制。还强调了来自人类生物监测研究的数据,这些研究涉及神经退行性疾病患者血浆中赭曲霉毒素A水平以及一些与年龄和性别相关的反应。此外,还综述了一些天然存在的生物活性化合物对抗赭曲霉毒素A神经毒性的神经治疗机制。总体而言,文献积累的数据表明,赭曲霉毒素A是一种神经毒素,可能在神经疾病中具有潜在的病理作用。开展前沿的原创转化研究以开发针对包括赭曲霉毒素A在内的食源性毒物相关神经毒性的神经治疗方法是必不可少的。

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