Gd-DTPA-induced dynamic metabonomic changes in rat biofluids

Objectives The purposes of this study were (1) to detect the dynamic metabonomic changes induced by gadopentetate dimeglumine (Gd-DTPA) and (2) to investigate the potential metabolic disturbances associated with the pathogenesis of nephrogenic systemic fibrosis (NSF) at the early stage. Methods A nuclear magnetic resonance (NMR)-based metabolomics approach was used to investigate the urinary and serum metabolic changes induced by a single tail vein injection of Gd-DTPA (dosed at 2 and 5   mmol/kg body weight) in rats. Urine and serum samples were collected on days 1, 2 and 7 after dosing. Results Metabolic responses of rats to Gd-DTPA administration were systematic involving changes in lipid metabolism , glucose metabolism , TCA cycle, amino acid metabolism and gut microbiota functions. Urinary and serum metabonomic recovery could be observed in both the 2 and 5   mmol/kg body weight group, but the metabolic effects of high-dosed (5   mmol/kg body weight) Gd-DTPA lasted longer. It is worth noting that hyperlipidemia was observed after Gd-DTPA injection, and nicotinate might play a role in the subsequent self-recovery of lipid metabolism. The disturbance of tyrosine , glutamate and gut microbiota metabolism might associate with the progression of NSF. Conclusion These findings offered essential information about the metabolic changes induced by Gd-DTPA, and could be potentially important for investigating the pathogenesis of NSF at the early stage. Moreover, the recovery of rats administrated with Gd-DTPA may have implications in the treatment of early stage NSF.