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伏马菌素B1的神经毒性:临床前证据、生化机制及治疗策略

Fumonisin B1 neurotoxicity: Preclinical evidence, biochemical mechanisms and therapeutic strategies.

作者信息

Obafemi Blessing A, Adedara Isaac A, Delgado Cássia Pereira, Obafemi Olabisi T, Aschner Michael, Rocha Joao B T

机构信息

Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Camobi, Santa Maria 97105-900, Brazil.

Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.

出版信息

Toxicol Rep. 2025 Jan 27;14:101931. doi: 10.1016/j.toxrep.2025.101931. eCollection 2025 Jun.

Abstract

The neurotoxic effects of fungal toxins in both humans and animals have been well documented. Fumonisin B1 (FB1), a mycotoxin produced by fungi of the species, is the most toxic fumonisin variant whose neurotoxic effect is still being elucidated. This review highlights the biochemical aspects of FB1 neurotoxicity, such as its mechanisms of action as well as therapeutic strategies. Both and studies have demonstrated that alteration in sphingolipid metabolism is a major event in FB-induced neurotoxicity. Studies have also shown that neurotoxicity due to FB1 involves dysregulation of several biochemical events in the brain, such as induction of oxidative stress and inflammation, mitochondrial dysfunction and associated programmed cell death, inhibition of acetylcholinesterase and alteration of neurotransmitter levels, decreased activity of NaK ATPase, as well as disruption of blood-brain barrier. This review highlights the potential public health effects of FB1-induced neurotoxicity and the need to limit human and animal exposure to FB1in order to prevent its neurotoxic effect. Moreover, it is hoped that this review would stimulate studies aimed at filling the current research gaps such as delineating the effect of FB1 on the blood-brain barrier and appropriate therapies for neurotoxicity caused by FB1.

摘要

真菌毒素对人类和动物的神经毒性作用已有充分记录。伏马菌素B1(FB1)是该种真菌产生的一种霉菌毒素,是毒性最强的伏马菌素变体,其神经毒性作用仍在研究中。这篇综述重点介绍了FB1神经毒性的生化方面,如作用机制和治疗策略。体外和体内研究均表明,鞘脂代谢改变是FB诱导神经毒性的主要事件。研究还表明,FB1引起的神经毒性涉及大脑中多个生化事件的失调,如氧化应激和炎症的诱导、线粒体功能障碍及相关程序性细胞死亡、乙酰胆碱酯酶的抑制和神经递质水平的改变、NaK ATP酶活性降低以及血脑屏障的破坏。这篇综述强调了FB1诱导神经毒性对公众健康的潜在影响,以及限制人类和动物接触FB1以预防其神经毒性作用的必要性。此外,希望这篇综述能激发相关研究,以填补当前的研究空白,如阐明FB1对血脑屏障的影响以及针对FB1引起的神经毒性的适当治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ab/11841125/0ff7a93c8ec6/gr1.jpg

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