Metabolomic Approach To Evaluate the Toxicological Effects of Nonylphenol with Rat Urine

Abstract

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.

Towards high-throughput metabolomics using ultrahigh-field Fourier transform ion cyclotron resonance mass spectrometry

“…Mass spectrometric techniques, including liquid chromatography--mass spectrometry (LC/ MS) (Allen et al 2003;Buchholz et al 2001;De Vos et al 2007;Wikoff et al 2007), gas chromatography--mass spectrometry (GC/MS) (Denkert et al 2006;Jones et al 2007; Lee et al 2007), and capillary electrophoresis--mass spectrometry (CE/MS) (Sato et al 2004;Soga et al 2006) are among the analytical techniques currently used in metabolomics research. These mass spectrometric techniques commonly use up-front separation steps to reduce the sample complexity and reduce suppression effects, thereby enhancing the detection sensitivity.…”

Proteomics and Metabolomics in Aortic Stenosis: Studying Healthy Valves for a Better Understanding of the Disease

“…In most cases, it is necessary a prior step for chemical derivatization of non-volatile and thermally stable metabolites. The two more used derivatization reagents include BSTFA (N, O-Bis (trimethylsilyl) trifluoroacetamide) and MSTFA (N-Methyl-N-(trimethylsilyl) trifluoroacetamide) [89][90][91]. Advantages of GC include higher resolution and more robust and reproducible retention times than LC, besides the existence of mass spectral libraries, which facilitates the identification process.…”

Heat-map visualization of gas chromatography-mass spectrometry based quantitative signatures on steroid metabolism

“…Quantitative metabolite profiling of urinary steroids was based on previous reports [4,8,32]. Briefly, urine samples (2 mL) spiked with 20 L of the 7 internal standards (d 3 -testosterone and d 4 -estradiol; 1 g/mL, d 4 -cortisol and d 8 -17␣-hydroxyprogesterone; 5 g/mL, methyltestosterone, d 9 -progesterone, and d 6 -cholesterol to 10 g/mL) were extracted with Oasis HLB SPE cartridges coupled to a peristaltic pump.…”

“…This technique promotes the establishment of relationships between phenotypes and metabolisms by providing descriptions of the distributions of metabolites and their biological functions. In fact, quantitative analyses of sets of metabolites in biochemical pathways have been used for physiological monitoring, toxicological evaluations, and clinical diagnosis [3][4][5][6].…”