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 5mmol/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 5mmol/kg body weight group, but the metabolic effects of high-dosed (5mmol/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.