Abstract
γ-Hydroxybutyric acid (GHB) is an endogenous short chain fatty acid that acts as a neurotransmitter and neuromodulator in the mammalian brain. It has often been illegally abused or misused due to its strong anesthetic effect, particularly in drug-facilitated crimes worldwide. However, proving its ingestion is not straightforward because of the difficulty in distinguishing between endogenous and exogenous GHB, as well as its rapid metabolism. Metabolomics and metabolism studies have recently been used to identify potential biomarkers of GHB exposure. This mini-review provides an overview of GHB-associated metabolic alterations and explores the potential of metabolites for application as biomarkers of GHB exposure. For this, we discuss the biosynthesis and metabolism of GHB, analytical issues of GHB in biological samples, alterations in metabolic pathways, and changes in the levels of GHB conjugates in biological samples from animal and human studies. Metabolic alterations in organic acids, amino acids, and polyamines in urine enable discrimination between GHB-ingested animals or humans and controls. The potential of GHB conjugates has been investigated in a variety of clinical settings. Despite the recent growth in the application of metabolomics and metabolism studies associated with GHB exposure, it remains challenging to distinguish between endogenous and exogenous GHB. This review highlights the significance of further metabolomics and metabolism studies for the discovery of practical peripheral biomarkers of GHB exposure.
Highlights
Metabolomics is a field of omics science that investigates changes in metabolites with molecular weights of 1500 Da or less in biological samples and aims to understand metabolic pathways related to abnormal conditions or diseases
Since GHB exists as a physiological compound in the human body, and exogenous GHB (ExGHB) exhibits the same physiological effects using almost the same neurobiological pathway as EnGHB, it is difficult to distinguish between
The results showed that single or multiple doses of GHB increased most of the OA, including GHB and D-2-HG, in the urine of rats (p < 0.05); in addition, the single dose group showed a greater increase in these factors than the multiple dose group
Summary
Metabolomics is a field of omics science that investigates changes in metabolites with molecular weights of 1500 Da or less in biological samples and aims to understand metabolic pathways related to abnormal conditions or diseases. Hair is more recently being used to monitor chronic drug use or chronic diseases, because it provides long detection windows, and segmental analysis of hair reflects the toxicological or pathological history [7]. Untargeted analysis is a method for analyzing the overall metabolic change in a selected biological sample, based on extensive information on unknown features, followed by the assignment of significantly altered features to specific metabolites. Metabolomics is currently being used to identify endogenous metabolites generated after exposure to addictive drugs [8,9,10,11] This metabolomics approach can provide a new foundation for identifying effective diagnostic markers or therapeutic targets, if the knowledge of the mechanisms of a drug’s pharmacodynamic or pharmacokinetic properties is limited [12]. One article [42] found in the reference list in one [34] of the searched articles was included since it is a metabolomics study of GHB
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