An insight into the metabolic responses of ultra-small superparamagnetic particles of ironoxide using metabonomic analysis of biofluids

Abstract

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed asintravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging(MRI) in vivo. However, their potential toxicity and effects on metabolism have attractedparticular attention. In the present study, uncoated and dextran-coated USPIOwere investigated by analyzing both rat urine and plasma metabonomes usinghigh-resolution NMR-based metabonomic analysis in combination with multivariatestatistical analysis. The wealth of information gathered on the metabolic profilesfrom rat urine and plasma has revealed subtle metabolic changes in response toUSPIO administration. The metabolic changes include the elevation of urinaryα-hydroxy-n-valerate,o- andp-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinaryα-ketoglutarate,succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. Thechanges associated with USPIO administration included a gradual increase in plasma glucose,N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such asphenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decreaseof myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administrationeffects are reflected in changes in a number of metabolic pathways including energy, lipid,glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolicresponses and possible toxicity were observed using NMR analysis of biofluids. Thesechanges may be attributed to the disturbances of hepatic, renal and cardiac functionsfollowing USPIO administrations. The potential biotoxicity can be derived frommetabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers apromising approach for the detection of subtle physiological responses on mammalianmetabolism, and can be employed to investigate the potential adverse effects ofother nanoparticles and nanomaterials on the environment and human health.