Abstract
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 10mgkg-1h-1 for 4h. 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 72-96h (for urine), and at 24 and 96h (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.
| Original language | English |
|---|---|
| Pages (from-to) | 29-37 |
| Number of pages | 9 |
| Journal | Toxicology |
| Volume | 287 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - Sep 5 2011 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Toxicology
Cite this
Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat. / Shima, Noriaki; Miyawaki, Izuru; Bando, Kiyoko; Horie, Hiroshi; Zaitsu, Kei; Katagi, Munehiro; Bamba, Takeshi; Tsuchihashi, Hitoshi; Fukusaki, Eiichiro.
In: Toxicology, Vol. 287, No. 1-3, 05.09.2011, p. 29-37.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat
AU - Shima, Noriaki
AU - Miyawaki, Izuru
AU - Bando, Kiyoko
AU - Horie, Hiroshi
AU - Zaitsu, Kei
AU - Katagi, Munehiro
AU - Bamba, Takeshi
AU - Tsuchihashi, Hitoshi
AU - Fukusaki, Eiichiro
PY - 2011/9/5
Y1 - 2011/9/5
N2 - 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 10mgkg-1h-1 for 4h. 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 72-96h (for urine), and at 24 and 96h (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.
AB - 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 10mgkg-1h-1 for 4h. 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 72-96h (for urine), and at 24 and 96h (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.
UR - http://www.scopus.com/inward/record.url?scp=79960699502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960699502&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2011.05.012
DO - 10.1016/j.tox.2011.05.012
M3 - Article
C2 - 21645582
AN - SCOPUS:79960699502
VL - 287
SP - 29
EP - 37
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 1-3
ER -