Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat

Noriaki Shima, Izuru Miyawaki, Kiyoko Bando, Hiroshi Horie, Kei Zaitsu, Munehiro Katagi, Takeshi Bamba, Hitoshi Tsuchihashi, Eiichiro Fukusaki

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 languageEnglish
Pages (from-to)29-37
Number of pages9
JournalToxicology
Volume287
Issue number1-3
DOIs
Publication statusPublished - Sep 5 2011
Externally publishedYes

Fingerprint

Metabolome
Methamphetamine
Rats
Citric Acid Cycle
Plasmas
Mass spectrometry
3-Hydroxybutyric Acid
Mass Spectrometry
Glucaric Acid
Pyrrolidonecarboxylic Acid
Glucose
Capillary electrophoresis
Glucose-6-Phosphate
Fumarates
Metabolomics
Uracil
Oxidative Phosphorylation
Liver Failure
Capillary Electrophoresis
Biomarkers

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Shima, N., Miyawaki, I., Bando, K., Horie, H., Zaitsu, K., Katagi, M., ... Fukusaki, E. (2011). Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat. Toxicology, 287(1-3), 29-37. https://doi.org/10.1016/j.tox.2011.05.012

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 journalArticle

Shima, N, Miyawaki, I, Bando, K, Horie, H, Zaitsu, K, Katagi, M, Bamba, T, Tsuchihashi, H & Fukusaki, E 2011, 'Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat', Toxicology, vol. 287, no. 1-3, pp. 29-37. https://doi.org/10.1016/j.tox.2011.05.012
Shima, Noriaki ; Miyawaki, Izuru ; Bando, Kiyoko ; Horie, Hiroshi ; Zaitsu, Kei ; Katagi, Munehiro ; Bamba, Takeshi ; Tsuchihashi, Hitoshi ; Fukusaki, Eiichiro. / Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat. In: Toxicology. 2011 ; Vol. 287, No. 1-3. pp. 29-37.
@article{4154937bc812498eaf1ce32f13f9f97c,
title = "Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat",
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.",
author = "Noriaki Shima and Izuru Miyawaki and Kiyoko Bando and Hiroshi Horie and Kei Zaitsu and Munehiro Katagi and Takeshi Bamba and Hitoshi Tsuchihashi and Eiichiro Fukusaki",
year = "2011",
month = "9",
day = "5",
doi = "10.1016/j.tox.2011.05.012",
language = "English",
volume = "287",
pages = "29--37",
journal = "Toxicology",
issn = "0300-483X",
publisher = "Elsevier Ireland Ltd",
number = "1-3",

}

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 -