Toxicometabolomics approach to urinary biomarkers for mercuric chloride (HgCl{sub 2})-induced nephrotoxicity using proton nuclear magnetic resonance ({sup 1}H NMR) in rats

Journal Article · Wed Dec 01 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.08.017· OSTI ID:21460245

Kim, Kyu-Bong ^[1]

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1. Korea Food and Drug Administration, 5-Nokbun-dong, Eunpyung-gu, Seoul 122-704 (Korea, Republic of)

The primary objective of this study was to determine and characterize surrogate biomarkers that can predict nephrotoxicity induced by mercuric chloride (HgCl{sub 2}) using urinary proton nuclear magnetic resonance ({sup 1}H NMR) spectral data. A procedure for {sup 1}H NMR urinalysis using pattern recognition was proposed to evaluate nephrotoxicity induced by HgCl{sub 2} in Sprague-Dawley rats. HgCl{sub 2} at 0.1 or 0.75 mg/kg was administered intraperitoneally (i.p.), and urine was collected every 24 h for 6 days. Animals (n = 6 per group) were sacrificed 3 or 6 days post-dosing in order to perform clinical blood chemistry tests and histopathologic examinations. Urinary {sup 1}H NMR spectroscopy revealed apparent differential clustering between the control and HgCl{sub 2} treatment groups as evidenced by principal component analysis (PCA) and partial least square (PLS)-discriminant analysis (DA). Time- and dose-dependent separation of HgCl{sub 2}-treated animals from controls was observed by PCA of {sup 1}H NMR spectral data. In HgCl{sub 2}-treated rats, the concentrations of endogenous urinary metabolites of glucose, acetate, alanine, lactate, succinate, and ethanol were significantly increased, whereas the concentrations of 2-oxoglutarate, allantoin, citrate, formate, taurine, and hippurate were significantly decreased. These endogenous metabolites were selected as putative biomarkers for HgCl{sub 2}-induced nephrotoxicity. A dose response was observed in concentrations of lactate, acetate, succinate, and ethanol, where severe disruption of the concentrations of 2-oxoglutarate, citrate, formate, glucose, and taurine was observed at the higher dose (0.75 mg/kg) of HgCl{sub 2}. Correlation of urinary {sup 1}H NMR PLS-DA data with renal histopathologic changes suggests that {sup 1}H NMR urinalysis can be used to predict or screen for HgCl{sub 2}-induced nephrotoxicity{sub .}

• OSTI ID: 21460245
• Journal Information: Toxicology and Applied Pharmacology, Vol. 249, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.08.017; PII: S0041-008X(10)00305-4; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL MARKERS
HYDROGEN 1
MERCURY CHLORIDES
NUCLEAR MAGNETIC RESONANCE
RATS
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CHLORIDES
CHLORINE COMPOUNDS
HALIDES
HALOGEN COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
MATERIALS
MERCURY COMPOUNDS
MERCURY HALIDES
NUCLEI
ODD-EVEN NUCLEI
RESONANCE
RODENTS
STABLE ISOTOPES
VERTEBRATES
WASTES