A metabonomic analysis of organ specific response to USPIO administration

Abstract

As ultrasmall superparamagnetic particles of iron oxides (USPIO) have been widely used in clinical medicine as MRI contrast agents, hence their potential toxicity and adverse effects following administration have attracted particular attention. In the present study, high resolution magic-angle-spinning (1)H NMR spectroscopy coupled with multivariate statistical analysis was used to directly determine the metabolic consequences of specific-tissues, including kidney, liver and spleen following the intravenous administration of USPIO. Alterations of renal, hepatic and splenic function were reflected by changes in a number of metabolic pathways including small molecules involved in energy, lipid, glucose, and amino acids metabolism. The toxicological potential and metabolic fate of USPIO seems to be linked to their surface chemistry and particle size. Hierarchical principal component analysis was used to explore the multidimensional metabolic relationships between various biological matrices such as kidney, liver, spleen, plasma and urine. Information on the involvement of USPIO in transportation, absorption, biotransformation, biodistribution and secretion was derived from metabolic correlation analysis between different organs and biofluids. Such a metabonomic strategy provides methodology for investigating the potential adverse biological effects of similar nanoparticles on the environmental and human health and assessing the drug interventions on the targeted organ.