title: Nanoparticulate silver increases uric acid and allantoin excretion in rats, as identified by metabolomics.
abstract: Metabolomic investigation of rat urine was employed to identify mammalian metabolites affected by ionic or nanoparticulate silver. Female and male Wistar rats were administered silver nanoparticles (2.25, 4.5 or 9.0 mg kg(-1) body weight per day) or ionic silver (silver acetate, 9.0 mg silver kg(-1) bw per day) by oral gavage for 28 days. On day 18, urine was collected for 24 h and subjected to metabolomics with high performance liquid chromatography-quadropole time-of-flight mass spectrometry (HPLC-QTOF-MS)-based separation and detection. Principal component analysis was subsequently applied to the data. Metabolomic differences in urine composition were found in female rats but not in male rats. Several metabolites were identified by the use of elemental composition calculated from the exact mass combined with searches in the Human Metabolome Database.The metabolite identities were eventually verified by co-chromatography with authentic standards. Differences were found in uric acid and its degradation product, allantoin. Administration of nanoparticulate silver increased both metabolites, whereas ionic silver only increased allantoin. In conclusion, metabolomic investigation of rat urine showed that increased levels of uric acid and allantoin were associated with exposure to nanoparticulate silver.
authors.affiliation: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860, Søborg, Denmark. niels.hadrup@gmail.com.
authors.forename: Niels
authors.initials: N
authors.lastname: Hadrup
authors.forename: Henrik R
authors.initials: HR
authors.lastname: Lam
authors.forename: Katrin
authors.initials: K
authors.lastname: Loeschner
authors.forename: Alicja
authors.initials: A
authors.lastname: Mortensen
authors.forename: Erik H
authors.initials: EH
authors.lastname: Larsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Frandsen
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000737:chemistry; D000481:Allantoin / Q000652:urine*; D000818:Animals; D005260:Female; D008297:Male; D055432:Metabolomics / Q000379:methods*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012834:Silver / Q000008:administration & dosage* / Q000737:chemistry; D018030:Silver Compounds / Q000008:administration & dosage / Q000737:chemistry; D014527:Uric Acid / Q000652:urine*
chemical_list: D000085:Acetates; D018030:Silver Compounds; C103100:silver acetate; D014527:Uric Acid; D000481:Allantoin; D012834:Silver