Lee Sang Hee, Woo Han Min, Jung Byung Hwa, Lee Jeongae, Kwon Oh Seung, Pyo Hee Soo, Choi Man Ho, Chung Bong Chul
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea.
Anal Chem. 2007 Aug 15;79(16):6102-10. doi: 10.1021/ac070237e. Epub 2007 Jul 18.
Metabolomics has focused on toxicological applications to (1) understand the mechanisms of toxicity, (2) identify novel biomarkers of toxicity, and (3) provide in vivo assessment in animal models through simple and fast methods to date. The toxicological effects of nonylphenol (NP) were evaluated after intraperitoneal injection of rats with 0, 50, and 250 mg kg(-1) day(-1) NP for four consecutive days. In the nontargeted approach, different extraction conditions were introduced to investigate the effects of NP on rats through gas chromatography/mass spectrometry (GC/MS). The GC/MS data obtained were further analyzed with partial least-squares discriminant analysis to compare toxicological effects between control and treated groups. The targeted approach was also used in combination with GC/MS to quantify endocrine hormones and to identify possible biomarkers in rat urine under optimal extraction conditions. In addition, we considered the metabolic trajectory to examine the metabolite profiles and patterns related to steroid metabolism in rats that were treated with NP, considering both treatment amount and time. The data suggest that tetrahydrocorticosterone and 5alpha-tetrahydrocorticosterone are possible urinary biomarkers of NP-induced toxicity. This metabolomic approach is a promising tool to assist with screening in toxicological studies.
代谢组学一直专注于毒理学应用，以（1）了解毒性机制，（2）识别新的毒性生物标志物，以及（3）迄今为止通过简单快速的方法在动物模型中进行体内评估。在连续四天给大鼠腹腔注射0、50和250 mg kg⁻¹天⁻¹的壬基酚（NP）后，评估了壬基酚的毒理学效应。在非靶向方法中，引入了不同的提取条件，通过气相色谱/质谱联用（GC/MS）研究NP对大鼠的影响。对获得的GC/MS数据进一步采用偏最小二乘判别分析，以比较对照组和处理组之间的毒理学效应。靶向方法也与GC/MS结合使用，以在最佳提取条件下定量内分泌激素并识别大鼠尿液中可能的生物标志物。此外，我们考虑了代谢轨迹，以研究与接受NP处理的大鼠类固醇代谢相关的代谢物谱和模式，同时考虑处理量和时间。数据表明，四氢皮质酮和5α-四氢皮质酮可能是NP诱导毒性的尿液生物标志物。这种代谢组学方法是毒理学研究中辅助筛选的一种有前景的工具。
