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乙醇和乙醛对斑马鱼脑结构的影响:关于谷氨酸摄取及毒性相关参数的体外研究方法

Effects of ethanol and acetaldehyde in zebrafish brain structures: an in vitro approach on glutamate uptake and on toxicity-related parameters.

作者信息

Zenki Kamila Cagliari, Mussulini Ben Hur Marins, Rico Eduardo Pacheco, de Oliveira Diogo Lösch, Rosemberg Denis Broock

机构信息

Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos, 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.

Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos, 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.

出版信息

Toxicol In Vitro. 2014 Aug;28(5):822-8. doi: 10.1016/j.tiv.2014.03.008. Epub 2014 Mar 27.

DOI:10.1016/j.tiv.2014.03.008
PMID:24681127
Abstract

Ethanol (EtOH) and its metabolite, acetaldehyde (ALD), induce deleterious effects on central nervous system (CNS). Here we investigate the in vitro toxicity of EtOH and ALD (concentrations of 0.25%, 0.5%, and 1%) in zebrafish brain structures [telencephalon (TE), opticum tectum (OT), and cerebellum (CE)] by measuring the functionality of glutamate transporters, MTT reduction, and extracellular LDH activity. Both molecules decreased the activity of the Na(+)-dependent glutamate transporters in all brain structures. The strongest glutamate uptake inhibition after EtOH exposure was 58% (TE-1%), and after ALD, 91% (CE-1%). The results of MTT assay and LDH released demonstrated that the actions of EtOH and its metabolite are concentration and structure-dependent, in which ALD was more toxic than EtOH. In summary, our findings demonstrate a differential toxicity in vitro of EtOH and ALD in zebrafish brain structures, which can involve changes on glutamatergic parameters. We suggest that this species may be an interesting model for assessing the toxicological actions of alcohol and its metabolite in CNS.

摘要

乙醇(EtOH)及其代谢产物乙醛(ALD)对中枢神经系统(CNS)具有有害影响。在此,我们通过测量谷氨酸转运体的功能、MTT还原以及细胞外乳酸脱氢酶(LDH)活性,研究了乙醇和乙醛(浓度分别为0.25%、0.5%和1%)对斑马鱼脑结构[端脑(TE)、视顶盖(OT)和小脑(CE)]的体外毒性。两种分子均降低了所有脑结构中钠依赖性谷氨酸转运体的活性。乙醇暴露后最强的谷氨酸摄取抑制率为58%(端脑-1%),乙醛暴露后为91%(小脑-1%)。MTT检测和LDH释放结果表明,乙醇及其代谢产物的作用具有浓度和结构依赖性,其中乙醛的毒性比乙醇更强。总之,我们的研究结果表明乙醇和乙醛在斑马鱼脑结构中具有不同的体外毒性,这可能涉及谷氨酸能参数的变化。我们认为该物种可能是评估酒精及其代谢产物在中枢神经系统中毒理作用的一个有趣模型。

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