کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2596014 | 1562370 | 2011 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat](/preview/png/2596014.png)
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.
Journal: Toxicology - Volume 287, Issues 1–3, 5 September 2011, Pages 29–37