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对叔丁基苯酚通过破坏斑马鱼的脂质代谢途径诱导肝脏脂质过度积累从而损害肝脏。

4-tert-Butylphenol impairs the liver by inducing excess liver lipid accumulation via disrupting the lipid metabolism pathway in zebrafish.

机构信息

Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

出版信息

Environ Pollut. 2024 Sep 1;356:124385. doi: 10.1016/j.envpol.2024.124385. Epub 2024 Jun 17.

DOI:10.1016/j.envpol.2024.124385
PMID:38897274
Abstract

Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to development, immunity, nerves, and reproduction. 4-tert-Butylphenol (4-t-BP) is disruptive to early zebrafish development, but its effects on zebrafish liver are unknown. In this study, the adverse effects of 4-t-BP on the liver were investigated using zebrafish as a model organism. 4-t-BP inhibited liver development in zebrafish embryos and induced liver damage in adult zebrafish. Even if F1 was not directly exposed to 4-t-BP, its growth and development were inhibited. 4-t-BP can lead to an increase in lipid accumulation, total cholesterol and triglycerides contents, and the activities of alanine transaminase and aspartate aminotransferase in zebrafish embryos and adult zebrafish livers, and also cause an acceleration of glucose metabolism in zebrafish embryos. In addition, qRT-PCR showed that 4-t-BP induced the changes in the expressions of liver development-, steroid and unsaturated fatty acid biosynthesis-, and glycerolipid and arachidonic acid metabolism-related genes in zebrafish embryos and inflammatory factors-, antioxidant enzymes- and lipid metabolism-related genes in adult zebrafish livers. Transcriptome sequencing of embryos showed that 4-t-BP altered the expressions of lipid metabolism pathways such as steroid and unsaturated fatty acid biosynthesis, glycerolipid, and arachidonic acid metabolism pathways. Therefore, 4-t-BP may be external stimuli that cause oxidative stress, inflammation, and lipid accumulation in zebrafish liver, resulting in tissue damage and dysfunction in zebrafish liver.

摘要

内分泌干扰化学物质(EDCs)可以通过干扰激素的合成和释放来破坏正常的内分泌功能,导致发育、免疫、神经和生殖系统的不良反应。4-叔丁基苯酚(4-t-BP)对早期斑马鱼的发育具有干扰作用,但对其肝脏的影响尚不清楚。本研究以斑马鱼为模型,探讨了 4-t-BP 对肝脏的不良影响。4-t-BP 抑制斑马鱼胚胎的肝脏发育,并诱导成鱼肝脏损伤。即使 F1 没有直接暴露于 4-t-BP,其生长和发育也受到抑制。4-t-BP 可导致斑马鱼胚胎和成鱼肝脏中脂质积累、总胆固醇和甘油三酯含量以及丙氨酸转氨酶和天冬氨酸转氨酶活性增加,并加速斑马鱼胚胎的葡萄糖代谢。此外,qRT-PCR 显示 4-t-BP 诱导了斑马鱼胚胎中肝脏发育、类固醇和不饱和脂肪酸生物合成以及甘油磷脂和花生四烯酸代谢相关基因以及成鱼肝脏中炎症因子、抗氧化酶和脂质代谢相关基因的表达变化。胚胎转录组测序表明,4-t-BP 改变了类固醇和不饱和脂肪酸生物合成、甘油磷脂和花生四烯酸代谢等脂质代谢途径的表达。因此,4-t-BP 可能是引起斑马鱼肝脏氧化应激、炎症和脂质积累的外部刺激物,导致斑马鱼肝脏组织损伤和功能障碍。

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