Potential surrogate markers for gamma-hydroxybutyrate administration may extend the detection window from 12 to 48 hours.
The exogenous administration of gamma-hydroxybutyrate (GHB) as a drug of abuse, and especially in date rape sexual assaults, has recently increased. Chromatographic techniques are used to detect GHB in blood or urine, with a window of detection limited to 12 h. This brief window makes the proof of administration problematic in most rape cases. This study is aimed to extend the window of detection through surrogate markers of GHB administration. Microarray technology is used in a DBA/2J mouse model to detect gene expression changes in peripheral blood after GHB exposure at times as long as 96 h post exposure. This study focuses on two of the most significantly altered transcripts, epiregulin and phosphoprotein enriched in astrocytes 15 (Pea-15). Both genes have increased the ribonucleic acid expression (8.5- and 4.6-fold upregulation at 96 h, respectively) in GHB-dosed mice (1 g/kg) as compared with the control. To confirm these results at the protein level, an intracellular flow cytometric assay is developed to detect protein level changes in the peripheral blood of both these potential biomarkers after GHB exposure. These results suggest that after further development, epiregulin and Pea-15 may prove to be significant surrogate markers in the indirect detection of GHB administration.
Larson
Scott J
SJ
Armed Forces Institute of Pathology, Washington, DC, USA.
Putnam
Elizabeth A
EA
Schwanke
Corbin M
CM
Pershouse
Mark A
MA
D000759:Adjuvants, Anesthesia / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers / Q000032:analysis; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000235:genetics; D066260:Epiregulin; D005260:Female; D053593:Forensic Toxicology / Q000379:methods*; D015870:Gene Expression / Q000187:drug effects; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012978:Sodium Oxybate / Q000032:analysis / Q000493:pharmacokinetics*; D015813:Substance Abuse Detection / Q000379:methods*
D000759:Adjuvants, Anesthesia; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C587880:EREG protein, human; D066260:Epiregulin; C587881:Ereg protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D004815:Epidermal Growth Factor; D012978:Sodium Oxybate