کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2596014 1562370 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat
چکیده انگلیسی

Methamphetamine (MA) is an illicit psychostimulant, and its abuse has become an international public health problem. MA intoxication can cause life-threatening hyperthermia, renal and liver failure, cardiac arrhythmias, and neurological damage. To investigate the relationship between the underlying mechanism of such intoxication and metabolic networks, mass spectrometry-based metabolomics experiments were performed on Sprague-Dawley rats treated with MA at 10 mg kg−1 h−1 for 4 h. Using a combination of gas chromatography–time-of-flight mass spectrometry and capillary electrophoresis–tandem mass spectrometry, global and targeted analyses were performed on biological samples collected during 0–24 and 72–96 h (for urine), and at 24 and 96 h (for plasma) after the last drug administration. Body temperature and plasma biochemical parameters were also measured to detect abnormal reactions in neuronal and other several tissues. 5-Oxoproline, saccharic acid, uracil, 3-hydroxybutyrate (3-HB), adipic acid, glucose, glucose 6-phosphate, fructose 1,6-bisphosphate, and tricarboxylic acid (TCA) cycle intermediates, such as fumarate, were proposed as potential biomarkers related to MA-induced intoxications. In particular, the observation of decreased TCA cycle intermediates and 3-HB and increased glucose suggested that high doses of MA inhibit biogenic energy production by glycolysis, oxidative phosphorylation via the TCA cycle, and the beta-oxidation of fatty acids. These results may provide not only a clue to clarify the underlying mechanism of diverse intoxication effects, but also biological fluid-based diagnostic and forensic methods with which to objectively demonstrate intoxication without directly determining the drug.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 287, Issues 1–3, 5 September 2011, Pages 29–37
نویسندگان
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