PMID- 25343288
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20151119
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 77
IP  - 22-24
DP  - 2014
TI  - Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles 
      in sprague-dawley male rats.
PG  - 1384-98
LID - 10.1080/15287394.2014.951755 [doi]
AB  - 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 (1)H-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.
FAU - Lee, Yu Kyung
AU  - Lee YK
AD  - a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
FAU - Park, Eun Young
AU  - Park EY
FAU - Kim, Shiwon
AU  - Kim S
FAU - Son, Ji Yeon
AU  - Son JY
FAU - Kim, Tae Hyung
AU  - Kim TH
FAU - Kang, Won Gu
AU  - Kang WG
FAU - Jeong, Tae Chun
AU  - Jeong TC
FAU - Kim, Kyu-Bong
AU  - Kim KB
FAU - Kwack, Seung Jun
AU  - Kwack SJ
FAU - Lee, Jaewon
AU  - Lee J
FAU - Kim, Suhkmann
AU  - Kim S
FAU - Lee, Byung-Mu
AU  - Lee BM
FAU - Kim, Hyung Sik
AU  - Kim HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Havcr1protein, rat)
RN  - 0 (Selenium-Binding Proteins)
RN  - 00BH33GNGH (Cadmium)
SB  - IM
MH  - Animals
MH  - Biomarkers/*urine
MH  - Cadmium/*toxicity
MH  - Cell Adhesion Molecules/urine
MH  - Chemokine CCL2/urine
MH  - Kidney/*drug effects/metabolism
MH  - Kidney Diseases/chemically induced
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - *Metabolome
MH  - Multivariate Analysis
MH  - Principal Component Analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Selenium-Binding Proteins/urine
EDAT- 2014/10/25 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/10/25 06:00
PHST- 2014/10/25 06:00 [entrez]
PHST- 2014/10/25 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.1080/15287394.2014.951755 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2014;77(22-24):1384-98. doi: 
      10.1080/15287394.2014.951755.