Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics

Krokos, Adamantios; Deda, Olga; Virgiliou, Christina; Gika, Helen; Raikos, Νikolaos; Aggelidou, Eleni; Κritis, Aristeidis; Theodoridis, Georgios

doi:10.3390/molecules26154610

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…A previous study determined the effects of psychostimulants on the metabolome profile in humans [36,37]. Serum samples were used extensively in prior metabolomics studies that investigated the effects of many diseases, such as Parkinson's disease [38], attention deficit/hyperactivity disorder [39], amyotrophic lateral sclerosis [40] and Alzheimer's disease [41].…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

et al. 2022

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Studies have demonstrated that chronic consumption of abused drugs induces alterations in several proteins that regulate metabolism. For instance, methamphetamine exposure reduces glucose levels. Fatty and amino acid levels were altered in groups exposed to abused drugs. Therefore, in our study, we investigated the serum metabolomic profile of patients diagnosed with cannabis and/or amphetamine use disorders. Blood was obtained from subjects (control, amphetamine, and cannabis). Detection of serum metabolites was performed using gas chromatography. The ratio peak areas for metabolites were analyzed across the three groups. Both cannabis and amphetamine groups showed higher d-erythrotetrafuranose, octadecanoic acid, hexadecenoic acid, trans-9-octadecanoic acid, lactic acid and methyl thio hydantoin metabolites compared with the control group. Moreover, cannabis patients were found to possess higher glycine, 9,12 octadecanoic acid malonic acid, phosphoric acid and prostaglandin F1a than controls. Our analysis showed that the identified metabolic profile of cannabis or amphetamine use disorder patients was different than control group. Our data indicated that chronic exposure to cannabis or amphetamine dysregulated metabolites in the serum. Future studies are warranted to explore the effects of these abused drugs on the metabolic proteins.

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Section: Introductionmentioning

confidence: 99%

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

et al. 2022

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“…The effect of using drugs of various natures was evaluated in 15 publications, [ 24 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Four publications studied the disturbance of the HepG2 metabolome after genetic editing [ 49 , 50 , 51 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

The Expectation and Reality of the HepG2 Core Metabolic Profile

et al. 2023

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To represent the composition of small molecules circulating in HepG2 cells and the formation of the “core” of characteristic metabolites that often attract researchers’ attention, we conducted a meta-analysis of 56 datasets obtained through metabolomic profiling via mass spectrometry and NMR. We highlighted the 288 most commonly studied compounds of diverse chemical nature and analyzed metabolic processes involving these small molecules. Building a complete map of the metabolome of a cell, which encompasses the diversity of possible impacts on it, is a severe challenge for the scientific community, which is faced not only with natural limitations of experimental technologies, but also with the absence of transparent and widely accepted standards for processing and presenting the obtained metabolomic data. Formulating our research design, we aimed to reveal metabolites crucial to the Hepg2 cell line, regardless of all chemical and/or physical impact factors. Unfortunately, the existing paradigm of data policy leads to a streetlight effect. When analyzing and reporting only target metabolites of interest, the community ignores the changes in the metabolomic landscape that hide many molecular secrets.

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“…One recent study used a metabolomics approach to study the effects of cocaine in the HepG2 hepatoma cell line, after exposure to 200 mM of the drug. Significant alterations to amino acid metabolic pathways (e.g., glycine, serine, threonine, arginine, proline, taurine) were observed, which were most marked in the cases of glutamate, aspartate and alanine [127]. A previous study, using a more metabolically competent model (Sprague-Dawley rats), analyzed plasma of cocaine-addicted animals (which were given a dose of 10 mg/Kg) and found significant changes to the levels of L-threonine, spermidine, cysteine and n-Propylamine [128].…”

Section: Livermentioning

confidence: 99%

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

Bravo

Faria

Brito-da-Costa

et al. 2022

Toxins

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Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

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Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics

Cited by 8 publications

References 42 publications

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

The Expectation and Reality of the HepG2 Core Metabolic Profile

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

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