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5-氨基乙酰丙酸对氯氰菊酯诱导的斑马鱼肝-肠-微生物群轴毒性的保护作用

Protective effects of 5-aminolevulinic acid against toxicity induced by alpha-cypermethrin to the liver-gut-microbiota axis in zebrafish.

作者信息

Cheng Yi, Zhang Jie, Gao Fei, Xu Yong, Wang Chengju

机构信息

Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.

出版信息

Ecotoxicol Environ Saf. 2022 Apr 1;234:113422. doi: 10.1016/j.ecoenv.2022.113422. Epub 2022 Mar 16.

DOI:10.1016/j.ecoenv.2022.113422
PMID:35305352
Abstract

To explore whether and how 5-aminolevulinic acid (ALA) can relieve the toxicity to the liver-gut-microbiota axis caused by alpha-cypermethrin (α-CP), adult zebrafish were exposed to α-CP (1.0 µg L) with or without 5.0 mg L ALA supplementation. In the present work, the calculated LC of α-CP+ALA was 1.15 μg L, increasing about 1.16-fold compared with that of α-CP group (0.99 μg L), which indicated that ALA can alleviate the toxicity of α-CP. ALA also alleviated the histopathological lesions in the liver and gut induced by α-CP. Transcriptome sequencing of the liver showed that ALA rescues the differential expression of genes involved in the oxidation-reduction, heme metabolism, and complement activation pathways associated with dysfunctions induced by α-CP, and these findings were verified by RT-qPCR analysis and detection of the activities of enzymes in the liver-gut axis. The gut microbiota 16S rRNA sequencing results showed that α-CP alone induced gut microbial dysbiosis, which was efficiently antagonized by ALA due to decreasing the relative abundances of Cetobacterium and 3 major pathogens, and increasing the relative abundances of beneficial genera. Taken together, the results indicate that ALA might be a promising candidate for attenuating the adverse effects caused by pesticide-induced environmental pollution.

摘要

为了探究5-氨基乙酰丙酸(ALA)是否以及如何缓解由氯氰菊酯(α-CP)对肝-肠-微生物群轴造成的毒性,将成年斑马鱼暴露于含有或不含有5.0 mg/L ALA补充剂的α-CP(1.0 μg/L)中。在本研究中,计算得出α-CP+ALA的LC为1.15 μg/L,与α-CP组(0.99 μg/L)相比增加了约1.16倍,这表明ALA可以减轻α-CP的毒性。ALA还减轻了由α-CP诱导的肝脏和肠道的组织病理学损伤。肝脏转录组测序表明,ALA挽救了与α-CP诱导的功能障碍相关的氧化还原、血红素代谢和补体激活途径中涉及的基因的差异表达,并且这些发现通过RT-qPCR分析以及肝-肠轴中酶活性的检测得到了验证。肠道微生物群16S rRNA测序结果表明,单独的α-CP会诱导肠道微生物失调,而ALA通过降低鲸杆菌属和3种主要病原体的相对丰度以及增加有益菌属的相对丰度有效地对抗了这种失调。综上所述,结果表明ALA可能是减轻农药诱导的环境污染所造成的不利影响的一个有前景的候选物。

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