Urinary metabolic fingerprinting for amiodarone-induced phospholipidosis in rats using FT-ICR MS.
In the research and development for new therapeutic compounds, there has been a focus on detecting the changes of metabolites induced by drug administration and finding surrogate markers to assess its toxicity. We examined the suitability of urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) for toxicological assessment in the amiodarone (AMD)-induced phospholipidosis (PLD) rat model. There were more than 400 different ion peaks detected in the negative ion mode analysis with FT-ICR MS. About 20% of the detected ions were altered more than 1.5 fold by AMD-treatment. On the scores plot of principal component analysis (PCA), the ion profiles of the treated were separated time-dependently. The loading plot revealed that the metabolites causing PCA results were m/z 178.05101, 191.01979, 192.06676, 212.00239, 258.9944 and 283.0820. The ion at m/z 178.05101 is considered to be hippurate (HA), 192.06676 is phenylacetylglycine (PAG) and 212.00239 is indican (IDN). These results indicate that PAG, IDN and HA are biomarkers for AMD-induced PLD in urinary metabolic fingerprinting using FT-ICR MS. These markers may be useful for evaluation of chemicals, which have the potential to induce PLD.
Hasegawa
Mina
M
Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
Takenaka
Shigeo
S
Kuwamura
Mitsuru
M
Yamate
Jyoji
J
Tsuyama
Shingo
S
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008064:Lipidoses / Q000139:chemically induced* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids / Q000652:urine*; D025341:Principal Component Analysis; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
D000889:Anti-Arrhythmia Agents; D015415:Biomarkers; D010743:Phospholipids; D000638:Amiodarone