کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2600514 1133269 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
1H NMR-based metabonomic investigation of tributyl phosphate exposure in rats
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
1H NMR-based metabonomic investigation of tributyl phosphate exposure in rats
چکیده انگلیسی

Tributyl phosphate (TBP) is a toxic organophosphorous compound widely used in many industrial applications, including significant usage in nuclear processing. The industrial application of this chemical is responsible for occupational exposure and environmental pollution. In this study, 1H NMR-based metabonomics has been applied to investigate the metabolic response to TBP exposure. Male Sprague-Dawley rats were given a TBP-dose of 15 mg/kg body weight, followed by 24 h urine collection, as was previously demonstrated for finding most of the intermediates of TBP. High-resolution 1H NMR spectroscopy of urine samples in conjunction with statistical pattern recognition and compound identification allowed for the metabolic changes associated with TBP treatment to be identified. Discerning NMR spectral regions corresponding to three TBP metabolites, dibutyl phosphate (DBP), N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, were identified in TBP-treated rats. In addition, the 1H NMR spectra revealed TBP-induced variations of endogenous urinary metabolites including benzoate, urea, and trigonelline along with metabolites involved in the Krebs cycle including citrate, cis-aconitate, trans-aconitate, 2-oxoglutarate, succinate, and fumarate. These findings indicate that TBP induces a disturbance to the Krebs cycle energy metabolism and provides a biomarker signature of TBP exposure. We show that three metabolites of TBP, dibutylphosphate, N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, which are not present in the control groups, are the most important factors in separating the TBP and control groups (p < 0.0023), while the endogenous compounds 2-oxoglutarate, benzoate, fumarate, trigonelline, and cis-aconetate were also important (p < 0.01).

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 199, Issue 1, 10 November 2010, Pages 10–16
نویسندگان
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