Gender-differentiated metabolic abnormalities of adult zebrafish with zinc pyrithione (ZPT) -induced hepatotoxicity

Zinc pyrithione (ZPT) is an extensively used microbicidal agent and its toxicity to multiple organs has been gradually recognized. However, details of the mechanism of ZPT toxicity are lacking and profile studies at metabolic level are still greatly limited. In this work we investigated the effects of ZPT on metabolic pathways of zebrafish liver after twenty-one days of exposure. Our integrated approach was underpinned by gas chromatography coupled with mass spectroscopy (GC-MS) and liver function analysis. Metabolomic profiles were generated from the livers of ZPT-treated zebrafish and 172 significantly altered metabolite peaks were detected. As a result, ZPT caused altered perturbation of metabolic pathways in male and female zebrafish liver. Moreover, ZPT induced the liver injury with the changes of the metabolites 2,4-diaminobutyric acid (2,4-DABA) with significant distinction between male and female zebrafish. ZPT caused gender-differentiated liver metabolic changes associated with the disruption of glycogenolysis and glycolysis metabolism, purine and pyrimidine metabolism, oxidative phosphorylation, arginine biosynthesis, and amino acid metabolism. Conclusively, exposure of ZPT may result in gender-differentiated metabolic abnormalities of adult zebrafish with induced hepatotoxicity. (C) 2020 Elsevier Ltd. All rights reserved.