Evaluation of Cadmium-Induced Nephrotoxicity Using Urinary Metabolomic Profiles in Sprague-Dawley Male Rats

Title
Evaluation of Cadmium-Induced Nephrotoxicity Using Urinary Metabolomic Profiles in Sprague-Dawley Male Rats
Author(s)
정태천이유경[이유경]박은영[박은영]김시원[김시원]손지연[손지연]김태형[김태형]강원구[강원구]김규봉[김규봉]곽승준[곽승준]이재원[이재원]김석만[김석만]이병무[이병무]김형식[김형식]
Keywords
SELENIUM-BINDING PROTEIN-1; INDUCED OXIDATIVE STRESS; PROXIMAL TUBULE INJURY; ZINC SUPPLEMENTATION; RISK-ASSESSMENT; EXPOSURE; KIDNEY; METALLOTHIONEIN; BIOMARKER; TOXICITY
Issue Date
201412
Publisher
TAYLOR & FRANCIS INC
Citation
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v.77, no.22-24, pp.1384 - 1398
Abstract
The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution H-1-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.
URI
http://hdl.handle.net/YU.REPOSITORY/30330http://dx.doi.org/10.1080/15287394.2014.951755
ISSN
1528-7394
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약학대학 > 약학부 > Articles
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