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Enantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposure

2026-02Artigo de investigação Acesso embargado
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dc.contributor.authorLanga, Ivan
dc.contributor.authorRocha-Pereira, Carolina
dc.contributor.authorSilva, Paula
dc.contributor.authorMilhazes, Nuno
dc.contributor.authorSilva, Diana Dias da
dc.contributor.authorDomingues, Susana
dc.contributor.authorResende, Albina Dolores
dc.contributor.authorBarbosa, Joana
dc.contributor.authorFaria, Juliana
dc.contributor.authorTiritan, Maria Elizabeth
dc.contributor.authorRibeiro, Cláudia
dc.date.accessioned2026-05-13T13:22:39Z
dc.date.available2026-05-13T13:22:39Z
dc.date.issued2026-02
dc.description.abstractynthetic cathinones are a class of new psychoactive substances (NPS) with 3-chloromethcathinone (3-CMC) accounting for over 46% of NPS-related seizures in 2023. Sold as a racemate, 3-CMC exhibits enantioselective metabolism and pharmacological effects, making enantioselectivity a critical factor in evaluating its toxicokinetics and toxicodynamics. This study aimed to evaluate the enantiomeric biodistribution, metabolic profile, and toxicity of 3-CMC racemate in Wistar rats following acute exposure. For this purpose, a gas chromatography–mass spectrometry (GC–MS) method was validated for quantifying 3-CMC in biological matrices and for characterizing its biodistribution in vivo. Rats were intraperitoneally administered with saline (control) or 3-CMC (10 or 20 mg kg−1, b.w.). Animals were sacrificed 24 h after administration, and plasma, urine, and tissues were collected for biodistribution, biochemical, and histopathological analyses. 3-CMC was exclusively detected in the urine, along with three additional pairs of enantiomeric metabolites. Both 3-CMC and its metabolites exhibit enantiomeric fractions (EF) different from 0.5, indicating enantiomeric enrichment. Administration of 3-CMC significantly decreased plasma levels of creatine kinase-MB, alkaline phosphatase, and aspartate aminotransferase, along with increased levels of glucose and urea. In the urine, decreased levels of albumin were observed. Oxidative stress and energy biomarkers were altered in the brain, lungs, and kidneys. Histopathological analysis revealed morphological alterations in the brain, liver, and lungs at both doses, and in the kidneys at the highest dose. However, no significant alterations were observed in the other tissues. Taken together, our findings suggest enantioselective metabolism and indicate that, although rapidly eliminated by the kidneys, 3-CMC still causes significant toxicity in target organs, such as the brain, liver, lungs, and kidneys. This highlights the high toxicity of the drug or its metabolites, even over short-term exposure.eng
dc.identifier.citationLanga, I., Rocha-Pereira, C., Silva, P., Milhazes, N., Silva, D. D. da, Domingues, S., Resende, A. D., Barbosa, J., Faria, J., Tiritan, M. E., & Ribeiro, C. (2026). Enantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposure. Journal of Analytical Toxicology, 50(2), 1–13. https://doi.org/10.1093/jat/bkaf103
dc.identifier.doi10.1093/jat/bkaf103
dc.identifier.eissn1945-2403
dc.identifier.issn0146-4760
dc.identifier.urihttp://hdl.handle.net/10400.22/32358
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford Academic
dc.relationPTDC/CTA-AMB/ 6686/2020-ENANTIOTOX
dc.relation.hasversionhttps://academic.oup.com/jat/article-abstract/50/2/bkaf103/8325234?redirectedFrom=fulltext
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectWistar rats
dc.titleEnantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposureeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage13
oaire.citation.issue2
oaire.citation.startPage1
oaire.citation.titleJournal of Analytical Toxicology
oaire.citation.volume50
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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