HIF-1α/HO-1-Mediated Ferroptosis Participates in Polystyrene Nanoplastics-Induced Intergenerational Cardiotoxicity
Ruiqiong Li, Xifeng Wang, Jinjin Zhang, Yinchu Hu, Yuxin Yang, Ying Zhang, Boqing Li, Meidi Shen, Chongkun Wang, Yuanyuan Yang, Xiaodong Song, Lihua Ren, Lianshuang Zhang
Abstract
To explore the intergenerational cardiotoxicity of nanoplastics, maternal mice were exposed to 60 nm polystyrene nanoplastics (PS-NP) during pregnancy and lactation. The results showed that PS-NP can enter the hearts of offspring and induce myocardial fiber arrangement disorder, acidophilic degeneration of cardiomyocytes, and elevated creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) levels after maternal exposure to PS-NP at 100 mg/kg during pregnancy and lactation. Mechanistically, KEGG analysis of RNA sequencing showed the participation of hypoxia-inducible factor-1 (HIF-1) and ferroptosis in PS-NP-induced cardiotoxicity. Key features of ferroptosis, including Fe 2+ accumulation, mitochondrial injury, oxidative stress, GPX4 downregulation, and FTH1, ACSL4, and SLC7A11 upregulation, were detected. Furthermore, PS-NP treatment upregulated the expressions of HIF-1α and HO-1, and PS-NP-induced ferroptosis can be alleviated by inhibition of HIF-1α using si-HIF-1α. This study provided an insightful reference for the intergenerational cardiotoxicity assessment of PS-NP.