title: Understanding the metabolic fate and assessing the biosafety of MnO nanoparticles by metabonomic analysis.
abstract: Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, (1)H NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development.
authors.affiliation: Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Electronic Science, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Li
authors.forename: Zhenghuan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jianghua
authors.initials: J
authors.lastname: Feng
authors.forename: Jinhao
authors.initials: J
authors.lastname: Gao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D001835:Body Weight; D016002:Discriminant Analysis; D016018:Least-Squares Analysis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017895:Manganese Compounds / Q000009:adverse effects* / Q000378:metabolism*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D053758:Nanoparticles / Q000009:adverse effects*; D009929:Organ Size; D009928:Organ Specificity; D010087:Oxides / Q000009:adverse effects* / Q000378:metabolism*; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014020:Tissue Extracts
chemical_list: D017895:Manganese Compounds; D010087:Oxides; D014020:Tissue Extracts; C027424:manganese oxide