Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7617853 | Journal of Chromatography B | 2014 | 6 Pages |
Abstract
4-Methylpiperazine-1-carbodithiocacid-3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208) was a potential antitumor new drug with many preliminary studies in pharmacokinetics and pharmacodynamics. This study aims to determine whether TM208 elicits toxic effects by metabonomics for the first time. Sprague Dawley (SD) rats were exposured to TM208 at a single therapeutic dose (100Â mg/kg/d) for 5 days, metabolites of urine samples from both control and TM208-treated groups were analyzed using high performance liquid chromatography-electrospray ionization source in combination with hybrid ion trap and high-resolution time-of-flight mass spectrometry (HPLC-ESI-IT-TOF/MS). Metabolites such as aminoadipic acid, creatine, gluconic acid, cis-aconitic acid, succinic acid and pipecolic acid which changed significantly, were identified as potential biomarkers. These results suggest that the changes in urinary metabolites of rats after exposure to TM208 were mainly related to energy metabolism and amino acid metabolism, which may be helpful to further understand the mechanism of TM208 toxicity in rats and a new drug development.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Haisong Yang, Wensi Lin, Jianmei Zhang, Weiwei Lin, Peng Xu, Jing Li, Xiaomei Ling,