Chan Seo1, Myungjin Na1, Jiyeun Jang1, Meejung Park2, Boyeon Choi3, Sooyeun Lee4, Man-Jeong Paik5. 1. College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. 2. National Forensic Service, 10 Ipchoon-ro, Wonju, Kangwon-do, 220-170, Republic of Korea. 3. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Taegu, 704-701, Republic of Korea. 4. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Taegu, 704-701, Republic of Korea. sylee21@kmu.ac.kr. 5. College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea. paik815@sunchon.ac.kr.
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.
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.
Entities:
Keywords:
Amino acid profiling analysis; Gas chromatography–mass spectrometry; Metabolomics; Star pattern analysis; γ-Hydroxybutyric acid
Authors: Tingting Wang; Kirstine L Nielsen; Kim Frisch; Johan K Lassen; Camilla B Nielsen; Charlotte U Andersen; Palle Villesen; Mette F Andreasen; Jørgen B Hasselstrøm; Mogens Johannsen Journal: Front Pharmacol Date: 2022-03-03 Impact factor: 5.810