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Monitoring of altered amino acid metabolic pattern in rat urine following intraperitoneal injection with γ-hydroxybutyric acid

Abstract

Introduction

γ-Hydroxybutyric acid is a well-known prescription medicine that is used for the clinical treatment of alcohol dependence and narcolepsy. However, the biochemical mechanism underlying γ-hydroxybutyric acid intoxication remains unclear, and metabolomic amino acid profiling and pattern analyses have not been attempted following treatment with γ-hydroxybutyric acid.

Objectives

We carried out urinary amino acid profiling and pattern analyses in rats to determine the biochemical events associated with altered amino acid metabolism and biomarker detection of intoxication following treatment with γ-hydroxybutyric acid.

Methods

Metabolic profiling analysis of amino acids in rat urine samples was performed as ethoxycarbonyl/tert-butyldimethylsilyl derivatives by gas chromatography–mass spectrometry following intraperitoneal administration of γ-hydroxybutyric acid once per day for 1 and 10 consecutive days.

Results

A total of 28 amino acids were positively identified in urine samples from the control, single and multiple groups treated with γ-hydroxybutyric acid. Their levels from the single and multiple treated groups were normalized to the corresponding mean control values. The star graphic pattern of the amino acids was characteristic and readily distinguishable for each group owing to its distorted nonacosagonal shape. In the principle component analysis, we monitored phenylalanine, glutamic acid, aspartic acid, asparagine, and methionine as contributing factors that discriminated the three groups.

Conclusion

The present metabolomic study may explain the altered metabolism of amino acids following administration, and intoxication with γ-hydroxybutyric acid.

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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1A6A1A03011325), by the Ministry of Science, ICT & Future Planning (2015R1A4A1041219) and by Suncheon Research Center for Natural Medicines.

Author information

MN and JJ performed sample preparation. CS performed GC–MS and data analyses. BC performed statistical analysis. MP, SL and MJP performed interpretation of the results. SL and MJP designed the study and supervised this work. MJP revised this paper. All of authors read and approved the final manuscript.

Correspondence to Sooyeun Lee or Man-Jeong Paik.

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Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the National Forensic Service.

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Seo, C., Na, M., Jang, J. et al. Monitoring of altered amino acid metabolic pattern in rat urine following intraperitoneal injection with γ-hydroxybutyric acid. Metabolomics 14, 111 (2018). https://doi.org/10.1007/s11306-018-1409-x

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Keywords

  • Metabolomics
  • γ-Hydroxybutyric acid
  • Amino acid profiling analysis
  • Star pattern analysis
  • Gas chromatography–mass spectrometry