Organ-Specific Metabolome Deciphering Cell Pathways to Cope with Mercury in Wild Fish (Golden Grey Mullet Chelon auratus)

SIMPLE SUMMARY: Metabolomics is a powerful approach that is based on the identification in biological samples of metabolites, which production and levels may vary due to factors intrinsic to the environment and the organism. For a correct data interpretation, it is, therefore, necessary to first evaluate the metabolome of the tissue/organ under investigation when it is exposed to no stressor. In this study, the complete set of metabolites of liver and gills of wild golden grey mullet (Chelon auratus) that were collected from a reference area was compared by using metabolomics, which was able to reveal metabolites that are commonly present in both organs but with different levels to be attributed to organ-specific functions. The same metabolomic approach was applied also to study the metabolite changes that were induced in mullet gills and liver after environmental exposure to mercury (Hg), and a variety of organ-specific metabolic disturbances were observed. The findings from this study validate the use of metabolomics in ecotoxicological studies to assess organ-specific functions and the cytotoxicity mechanisms of Hg in fish. ABSTRACT: Metabolomics is a powerful approach in evaluating the health status of organisms in ecotoxicological studies. However, metabolomics data reflect metabolic variations that are attributable to factors intrinsic to the environment and organism, and it is thus crucial to accurately evaluate the metabolome of the tissue/organ examined when it is exposed to no stressor. The metabolomes of the liver and gills of wild golden grey mullet (Chelon auratus) from a reference area were analyzed and compared by proton nuclear magnetic resonance ((1)H NMR)-based metabolomics. Both organs were characterized by amino acids, carbohydrates, osmolytes, nucleosides and their derivatives, and miscellaneous metabolites. However, similarities and differences were revealed in their metabolite profile and related to organ-specific functions. Taurine was predominant in both organs due to its involvement in osmoregulation in gills, and detoxification and antioxidant protective processes in liver. Environmental exposure to mercury (Hg) triggered multiple and often differential metabolic alterations in fish organs. Disturbances in ion-osmoregulatory processes were highlighted in the gills, whereas differential impairments between fish organs were pointed out in energy-producing metabolic pathways, protein catabolism, membrane stabilization processes, and antioxidant defense system, reflecting the induction of organ-specific adaptive and defensive strategies. Overall, a strict correlation between metabolites and organ-specific functions of fish gills and liver were discerned in this study, as well as organ-specific cytotoxicity mechanisms of Hg in fish.