Uncovering Spatially Resolved 6PPDQ Metabolism in Rainbow Trout Fry with Nano-DESI Mass Spectrometry Imaging

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine
quinone
(6PPDQ) is an emerging tire-derived contaminant that poses a critical
environmental risk to select salmonids. However, the mechanisms of
6PPDQ toxicity are currently unresolved. While species-specific metabolomic
effects of 6PPDQ exposure have been explored, to our knowledge no
studies have investigated the in situ spatial distribution
of 6PPDQ and 6PPDQ biotransformation products in salmonids. Herein,
we employ nanospray desorption electrospray ionization (nano-DESI)
mass spectrometry imaging (MSI) to visualize 6PPDQ metabolism in 6-week
posthatch rainbow trout fry exposed to 0.61 μg/L of 6PPDQ for
96 h. These data provide the first spatial mapping of 6PPDQ metabolism
in fishes. 6PPDQ was not observed in any fish tissues; however, primary
6PPDQ biotransformation products, hydroxylated 6PPDQ and dihydroxylated
6PPDQ, were found to localize in the liver and gut of exposed fry.
Additionally, interrogation of nontargeted nano-DESI spatial metabolomics
revealed an accumulation of free fatty acids in the central nervous
system of exposed fry. Overall, this study uncovers the spatially
resolved 6PPDQ metabolism in exposed fishes and explores the disparate
localization of endogenous metabolites disrupted by 6PPDQ exposure.