1H NMR-based serum metabolic profiling of Carassius auratus gibelio under the toxicity of Pb2+ and Cd2+

Lead and cadmium are the two widely recognized toxic metals, with known ecological risk to freshwater fish in contaminated ecosystems. However, their effect at environmentally realistic level in a mixture has been rarely investigated. In the present study, serum metabolic responses of Crucian carp exposed to Pb (30 µgL^?1), Cd (100 µgL^?1) and Pb+Cd (30 + 100 µgL^?1) for 21 days were investigated by ¹H NMR-based metabolomics. The metabolic responses were compared to control by multivariate techniques (PCA, PLS-DA and OPLS-DA), and metabolites that significantly contributed to the variation were identified. Metal dependent metabolic responses revealed a decline of alanine, lysine and tyrosine in Pb exposed fish, indicating changes in neurotransmitters, and amino acid metabolism, while fish exposed to Cd showed significant decrease in lysine, isoleucine, leucine, alanine and increase in 3-hydroxybutyrate, acetone, lactate, choline, inosine, guanosine and threonine. The coexposure of Pb and Cd had additive effect on metabolic profile with increase in pyruvate, guanosine and inosine. The overall metabolic changes due to Pb and Cd were characterized by disturbed energy metabolism, impaired osmotic regulation and a shift from aerobic to anaerobic respiration. Moreover, ¹H NMR-based metabolomics was proved to be a powerful tool in elucidating the toxic effects of environmental pollutants and underlying mechanism.