Characterization of N-(1,3-dimethylbutyl)-N '-phenyl-p-phenylenediamine (6PPD)-induced cardiotoxicity in larval zebrafish (Danio rerio)

文献类型： 外文期刊

第一作者： Fang, Chanlin

作者： Fang, Chanlin;Fang, Liya;Yu, Yundong;Wang, Caihong;Jin, Yuanxiang;Di, Shanshan;Yu, Yundong;Wang, Xinquan

作者机构：

关键词： 6PPD; Zebrafish larvae; Cardiotoxicity; Oxidative stress; Apoptosis

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：9.8； 五年影响因子：9.6 ）

ISSN： 0048-9697

年卷期： 2023 年 882 卷

页码：

收录情况： SCI

摘要： N-(1,3-dimethylbutyl)-N '-phenyl-p-phenylenediamine (6PPD) is a type of p-phenylenediamine (PPD), which is widely used in the manufacture of rubber tires owing to its excellent antiozonant properties. In this study, the developmental cardiotoxicity of 6PPD was evaluated in zebrafish larvae, and the LC50 was approximately 737 mu g/L for the larvae at 96 h post fertilization (hpf). In the 6PPD treatment of 100 mu g/L, the accumulation concentrations of 6PPD were up to 2658 ng/g in zebrafish larvae, and 6PPD induced significant oxidative stress and cell apoptosis in the early developmental stages of zebrafish. Transcriptome analysis showed that 6PPD exposure could potentially cause cardiotoxicity in larval zebrafish by affecting the transcription of the genes related to the calcium signal pathway and cardiac muscle contraction. The genes related to calcium signaling pathway (slc8a2b, cacna1ab, cacna1da, and pln) were verified by qRT-PCR, which were significantly downregulated in larval zebrafish after exposing to 100 mu g/L of 6PPD. Simultaneously, the mRNA levels of the genes related to cardiac functions (myl7, sox9, bmp10, and myh71) also respond accordingly. H&E staining and heart morphology investigation indicated that cardiac malformation occurred in zebrafish larvae exposed to 100 mu g/L of 6PPD. Furthermore, the phenotypic observation of transgenic Tg (myl7: EGFP) zebrafish also confirmed that 100 mu g/L of 6PPD exposure could change the distance of atria and ventricles of the heart and inhibit some key genes (cacnb3a, ATP2a1l, ryr1b) related to cardiac function in larval zebrafish. These results revealed the toxic effects of 6PPD on the cardiac system of zebrafish larvae.

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