Mass Spectrometry Imaging Unveils the Metabolic Effect of 6PPD-Quinone in Exposed Mice

Abstract

<i>N</i>-(1,3-dimethylbutyl)-<i>N</i>'-phenyl-<i>p</i>-phenylenediamine quinone (6PPD-Q) has gained widespread attention as an emerging significant environmental contaminant, but its biochemical toxicity in mammals remains inadequately explored. In this study, the systemic toxicological effects of 6PPD-Q in mouse models exposed to both high and low doses were investigated. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied to evaluate its effects on major organs, including the liver, kidneys, spleen, and testes. Notably, both high and low doses caused similar multiorgan metabolic disturbances, with significant changes in antioxidant levels, highlighting oxidative stress as a key factor in 6PPD-Q-induced damage. Further results revealed that 6PPD-Q disrupts critical metabolic pathways, including glutathione metabolism, ascorbic acid metabolism, energy metabolism, and amino acid metabolism, which are associated with systemic oxidative stress, immune dysfunction, and disruptions in liver, kidney and testis. This study provides important insights into the mechanisms of 6PPD-Q toxicity and underscores the need for further research to assess its potential health risks, which could guide future environmental policies and human health risk assessments.