The potential biomarkers of drug addiction: proteomic and metabolomics challenges

Lv, Wang; Wu, Ning; Zhao, Tai-Yun; Li, Jin

doi:10.1080/1354750x.2016.1201530

Cited by 20 publications

(16 citation statements)

References 55 publications

(50 reference statements)

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“…13 So far, few studies have focused on drugs of abuse (DOA) [14][15][16][17][18] and many of those were performed on mice and rats. Biomarker research can be used for acute or chronic drug consumption to investigate consumption behavior or to find underlying toxicological aspects of its action in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Biomarker research can be used for acute or chronic drug consumption to investigate consumption behavior or to find underlying toxicological aspects of its action in humans. 13 So far, few studies have focused on drugs of abuse (DOA) [14][15][16][17][18] and many of those were performed on mice and rats. [19][20][21][22] Metabolites such as 5-oxoproline, saccharic acid, uracil, and others showed to be indicative of methamphetamine intoxication.…”

Section: Introductionmentioning

confidence: 99%

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Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Boxler

Schneider

Kræmer

et al. 2018

Drug Testing and Analysis

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Over the past few years, the interest in metabolomics has increased in various fields including forensic toxicology. Forensic analysis typically requires a high degree of accuracy, which is often a problem in metabolomics applications. We aimed for a systematic evaluation of different analytical considerations of a metabolomics workflow allowing a targeted approach within an untargeted setup. Samples with 69 metabolites from different chemical classes were qualitatively and quantitatively analyzed on a high resolution quadrupole time of flight mass spectrometer coupled to liquid chromatography (UHPLC-QTOF). Three issues were addressed: (a) Two different approaches on "blind matrix" a simulated body fluid (SBF) and plasma-filtrate, were tested for calibration samples; (b) comparison of two different HPLC columns, reverse-phase (RP) and hydrophilic interaction chromatography (HILIC); and (c) comparison of three different acquisition modes (TOF-MS, information dependent data acquisition (IDA), and sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Samples were measured repeatedly for method comparison based on sensitivity, accuracy, precision, and detection robustness. The blind matricesshowed similar accuracy for most analytes, while SBF provided an easier preparation with satisfying results. To cover a wide part of the human metabolome, a combination of RP and HILIC showed the best results. The different scan modes performed equally regarding metabolite quantification while TOF-MS was more sensitive but lacked MS/MS spectra generation. IDA and SWATH files were aligned to various databases where IDA showed good MS/MS spectra matches. SWATH seemed to be beneficial in detection rate but was incompatible with many important software tools in metabolomics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Boxler

Schneider

Kræmer

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…For the estimation of the postmortem interval (PMI), metabolomics studies found elevated levels of amino acids and creatinine postmortem (Castillo-Peinado and Luque de Castro, 2016) and decreasing levels of sterol sulfates and very-long-chain fatty acids within the postmortem period (Wood and Shirley, 2014). Additionally, biomarker research within the field of forensic toxicology might successfully be used to investigate consumption behavior, to distinguish between acute or chronic drug consumption or to find the underlying mode of toxicological action in humans (Wang et al, 2016a). Thereby, different applications of metabolomics strategies in biomarker research for DOA identification were proposed: (a) as an additional tool for metabolism studies bearing the major advantage that particularly a priori unknown or unexpected metabolites can be identified; and (b) for identification of endogenous biomarker or metabolite patterns, e.g., for synthetic cannabinoids or also to indirectly detect urine manipulation attempts such as artificial urine samples or chemical adulteration.…”

Section: Metabolomicsmentioning

confidence: 99%

Metabolomic Strategies in Biomarker Research–New Approach for Indirect Identification of Drug Consumption and Sample Manipulation in Clinical and Forensic Toxicology?

2019

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Drug of abuse (DOA) consumption is a growing problem worldwide, particularly with increasing numbers of new psychoactive substances (NPS) entering the drug market. Generally, little information on their adverse effects and toxicity are available. The direct detection and identification of NPS is an analytical challenge due to their ephemerality on the drug scene. An approach that does not directly focus on the structural detection of an analyte or its metabolites, would be beneficial for this complex analytical scenario and the development of alternative screening methods could help to provide fast response on suspected NPS consumption. A metabolomics approach might represent such an alternative strategy for the identification of biomarkers for different questions in DOA testing. Metabolomics is the monitoring of changes in small (endogenous) molecules (<1,000 Da) in response to a certain stimulus, e.g., DOA consumption. For this review, a literature search targeting “metabolomics” and different DOAs or NPS was conducted. Thereby, different applications of metabolomic strategies in biomarker research for DOA identification were identified: (a) as an additional tool for metabolism studies bearing the major advantage that particularly a priori unknown or unexpected metabolites can be identified; and (b) for identification of endogenous biomarker or metabolite patterns, e.g., for synthetic cannabinoids or also to indirectly detect urine manipulation attempts by chemical adulteration or replacement with artificial urine samples. The majority of the currently available literature in that field, however, deals with metabolomic studies for DOAs to better assess their acute or chronic effects or to find biomarkers for drug addiction and tolerance. Certain changes in endogenous compounds are detected for all studied DOAs, but often similar compounds/pathways are influenced. When evaluating these studies with regard to possible biomarkers for drug consumption, the observed changes appear, albeit statistically significant, too small to reliably work as biomarker for drug consumption. Further, different drugs were shown to affect the same pathways. In conclusion, metabolomic approaches possess potential for detection of biomarkers indicating drug consumption. More studies, including more sensitive targeted analyses, multi-variant statistical models or deep-learning approaches are needed to fully explore the potential of omics science in DOA testing.

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“…Metabolomics was probably the last "-omics" approach to be employed in drug addiction studies. The pioneering metabolomic studies aimed to find plasma metabolites that behave like biomarkers, both in diagnosis or to help understand the processes underlying drug addiction [6,7]. Plasma and urine samples from rats subjected to a CPP paradigm with cocaine, amphetamine and morphine have been analyzed using metabolomics techniques, demonstrating that cocaine affected four metabolites: L-threonine (L-Thr), cysteine, n-propylamine and spermidine.…”

Section: Introductionmentioning

confidence: 99%

The effects of combined intravenous cocaine and ethanol self-administration on the behavioral and amino acid profile of young adult rats

et al. 2020

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Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels.

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The potential biomarkers of drug addiction: proteomic and metabolomics challenges

Cited by 20 publications

References 55 publications

Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Metabolomic Strategies in Biomarker Research–New Approach for Indirect Identification of Drug Consumption and Sample Manipulation in Clinical and Forensic Toxicology?

The effects of combined intravenous cocaine and ethanol self-administration on the behavioral and amino acid profile of young adult rats

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