|
KMID : 0606920110190010038
|
|
Biomolecules & Therapeutics
2011 Volume.19 No. 1 p.38 ~ p.44
|
|
|
Identification of Urinary Biomarkers Related to Cisplatin-Induced Acute Renal Toxicity Using NMR-Based Metabolomics
|
|
Wen He
Yang Hye-Ji
Choi Myung-Joo
Kwon Hyuk-Nam
Kim Min-Ah
Hong Soon-Sun
Park Sung-Hyouk
|
|
|
Abstract
|
|
|
|
Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identifi ed urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures- Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were signifi cantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.
|
|
|
KEYWORD
|
|
|
Cisplatin, Toxicity, NMR, OPLS-DA
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|