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6PPD induced cardiac dysfunction in zebrafish associated with mitochondrial damage and inhibition of autophagy processes

文献类型： 外文期刊

作者： Fang, Chanlin 1 ; Di, Shanshan 2 ; Yu, Yundong 1 ; Qi, Peipei 2 ; Wang, Xinquan 2 ; Jin, Yuanxiang 1 ;

作者机构： 1.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Peoples R China

2.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, State Key Lab Managing Biot & Chem Threats Qual &, Key Lab Detect Pesticide Residues & Control Zhejia, Hangzhou 310021, Peoples R China

3.Desheng Middle Rd 298, Hangzhou 310021, Zhejiang, Peoples R China

4.Chaowang Rd 18, Hangzhou, Zhejiang, Peoples R China

关键词： 6PPD exposure; Adult zebrafish; Cardiac dysfunction; Mitochondrial apoptosis; Autophagy

期刊名称：JOURNAL OF HAZARDOUS MATERIALS （ 影响因子：13.6； 五年影响因子：12.7 ）

ISSN： 0304-3894

年卷期： 2024 年 471 卷

页码：

收录情况： SCI

摘要： The compound 6PPD is widely acknowledged for its antioxidative properties; however, concerns regarding its impact on aquatic organisms have spurred comprehensive investigations. In our study, we advanced our comprehension by revealing that exposure to 6PPD could induce cardiac dysfunction, myocardial injury and DNA damage in adult zebrafish. Furthermore, our exploration unveiled that the exposure of cardiomyocytes to 6PPD resulted in apoptosis and mitochondrial injury, as corroborated by analyses using transmission electron microscopy and flow cytometry. Significantly, our study demonstrated the activation of the autophagy pathway in both the heart of zebrafish and cardiomyocytes, as substantiated by transmission electron microscopy and immunofluorescent techniques. Importantly, the increased the expression of P62 in the heart and cardiomyocytes suggested an inhibition of the autophagic process. The reduction in autophagy flux was also verified through in vivo experiments involving the infection of mCherry-GFP-LC3. We further identified that the fusion of autophagosomes and lysosomes was impaired in the 6PPD treatment group. In summary, our findings indicated that Journal of Hazardous Materials 471 (2024) 134357 the impaired fusion of autophagosomes and lysosomes hampered the autophagic degradation process, leading to apoptosis and ultimately resulting in cardiac dysfunction and myocardial injury. This study discovered the crucial role of the autophagy pathway in regulating 6PPD-induced cardiotoxicity. Synopsis: 6PPD exposure inhibited the autophagic degradation process and induced mitochondrial injury and apoptosis in the heart of adult zebrafish.

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