Multidimensional measurement of 6-PPDQ exposure aggravates myocardial injury in mice

The toxicity of the contaminant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6-PPDQ) is a growing concern. However, its potential myocardial toxicity remains unclear. In this study, the impact of 6-PPDQ on myocardial tissue was investigated. Differential RNA expression profiles and metabolic patterns in myocardial tissues from 6-PPDQ–exposed and untreated mice were examined using whole-transcriptome sequencing and untargeted metabolomics based on RNA sequencing and ultra-high-performance liquid chromatography. Our results showed that 6-PPDQ induces myocardial damage by exacerbating pathological changes, elevating cardiac injury biomarker levels, and increasing cardiomyocyte apoptosis. Transcriptome analysis revealed differentially expressed long noncoding RNAs (501), circular RNAs (138), microRNAs (63), and mRNAs (4054) in the 6-PPDQ group compared with the controls. Metabolomic analysis revealed 208 differential metabolites, along with dysregulation of ABC transporters, the citrate cycle, and efferocytosis. Integrated whole-transcriptome and untargeted metabolomics profiling presented Myl7, Orm1, Usp29, and Rxfp1 were participated in 6-PPDQ induces myocardial injury. Finally, Myl7 was identified as the potential candidate target of 6-PPDQ through molecular docking and expression analyses, and molecular dynamics (MD) simulations. These findings collectively indicate that 6-PPDQ exacerbates cardiac damage partially through the dysregulation of Myl7 expression, highlighting the mechanisms underlying its myocardial toxicity.