Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish

Markin, Pavel A.; Brito, Alex; Moskaleva, Natalia E.; Tagliaro, Franco; Frano, Michael R. La; Savitskii, Mark V.; Appolonova, Svetlana A.

doi:10.1016/j.cbpc.2021.109000

Cited by 7 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results were based on the identification of the biochemical features detected in the blood. We recently reported that the short- and long-term exposures of 5F-APINAC in a zebrafish model were mainly characterized by alterations in the kynurenine pathway but, also, in other neurotransmitter systems such as the gamma-aminobutyric acid/glutamic acid, dopaminergic/adrenergic and cholinergic neurotransmitter systems not found to be altered in rabbit plasma [ 8 ]. This may be explained by the fact that these alterations were measured in the entire organism of the zebrafish, reflecting the systemic biochemical alterations from the organs and not just from the blood, as in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, due to the rapid metabolism of 5F-APINAC, the parent drug has not been detected so far in urine. In a zebrafish model, the short- and long-term exposures of 5F-APINAC induced metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity [ 8 ]. However, to our knowledge, the pharmacokinetics properties of 5F-APINAC, as well as the influence of this drug on mammal neurotransmitter metabolisms, have not been characterized yet.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0–24 h). Ultra-high-performance liquid chromatography–tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, the Fish Embryo Acute Toxicity (FET) Test (TG 236) outlines an acute embryonic exposure design from 0–96 hpf, which covers the organogenesis period [ 17 ]. For zebrafish metabolomics studies, short-term exposure effects could be assessed in terms of hours (e.g., 2.5–4 h; as described in, e.g., TG 236 in embryos and TG 203 in adult fish) or medium- to long-term exposures in the larval period (e.g., 3–7 days) [ 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. For chronic exposure, test guidelines are available for larval fish up to 30 days (e.g., TG 210) and for adult fish up to 20 or 60 days (e.g., TGs 229 and 234), when individually dissected fish tissues (e.g., liver, brain, intestinal samples, gonads) or blood samples could be analyzed [ 25 , 26 , 27 ].…”

Section: Experimental Designmentioning

confidence: 99%

Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges

et al. 2021

View full text Add to dashboard Cite

Metabolomics has achieved great progress over the last 20 years, and it is currently considered a mature research field. As a result, the number of applications in toxicology, biomarker, and drug discovery has also increased. Toxicometabolomics has emerged as a powerful strategy to provide complementary information to study molecular-level toxic effects, which can be combined with a wide range of toxicological assessments and models. The zebrafish model has gained importance in recent decades as a bridging tool between in vitro assays and mammalian in vivo studies in the field of toxicology. Furthermore, as this vertebrate model is a low-cost system and features highly conserved metabolic pathways found in humans and mammalian models, it is a promising tool for toxicometabolomics. This short review aims to introduce zebrafish researchers interested in understanding the effects of chemical exposure using metabolomics to the challenges and possibilities of the field, with a special focus on toxicometabolomics-based mass spectrometry. The overall goal is to provide insights into analytical strategies to generate and identify high-quality metabolomic experiments focusing on quality management systems (QMS) and the importance of data reporting and sharing.

show abstract

“…In the present study, we have used diazepam as a reference standard for the evaluation of an anxiolytic activity. There are also studies on Zebrafish larvae proving that diazepam increases the level of serotonin and tryptophan in a dose-dependent manner after 2.5 h of bathing in the tested solution [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Incorporation of Different dn-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties

Rogalewicz

Szczesio

Poleszak

et al. 2021

IJMS

View full text Add to dashboard Cite

Three new compounds, namely [HL]2+[CuCl4]2−, [HL]2+[ZnCl4]2−, and [HL]2+[CdCl4]2− (where L: imipramine) were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which have been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined. Magnetic measurements were performed in order to study the magnetic properties of the compounds. The above mentioned techniques allowed us to comprehensively examine the physicochemical properties of the newly obtained compounds. The biological activity was investigated using the number of Zebrafish tests, as it is one of the most common models for studying the impact of newly synthesized compounds on the central nervous system (CNS), since this model is very similar to the human CNS.

show abstract

Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish

Cited by 7 publications

References 54 publications

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges

Influence of Incorporation of Different dn-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties

Contact Info

Product

Resources

About