The role of mitochondrial dysfunction and calcium dysregulation in 2C-I and 25I-NBOMe-induced neurotoxicity
Rattachement africain : pt. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
New psychoactive substances (NPS) are designed to evade legal regulation while mimicking the effects of classic illicit drugs such as 3,4-methylenedioxymethamphetamine (MDMA). This category includes phenethylamine derivatives, such as the psychedelic 2C and NBOMe drugs. Given the lack of data regarding the toxicological profile of these substances, the goal of this study was to evaluate the neurotoxicity of 2C-I and 25I-NBOMe and explore their neurotoxic pathways. Lower EC 50 values, in both NR uptake and MTT reduction assays in differentiated SH-SY5Y cells and primary rat cortical cultures, revealed that 25I-NBOMe is significantly more cytotoxic than 2C-I, likely due to its higher lipophilicity. Both drugs triggered severe mitochondrial dysfunction, characterized by decreased intracellular ATP levels and mitochondrial membrane depolarization, although no significant changes in intracellular ROS/RNS levels were observed. Additionally, 25I-NBOMe increased the intracellular Ca 2 ⁺ levels. Apoptosis was an observed mechanism of cell death for both drugs, as demonstrated by a significant increase in the number of cells undergoing early apoptosis (AnV + /PI − ) and late apoptosis/necrosis (AnV + /PI + ). However, only 2C-I induced autophagy and strongly triggered caspase-3 activation. This suggests that 2C-I induces caspase-3-dependent apoptosis, whereas 25I-NBOMe may also induce apoptosis through a caspase-3-independent pathway, possibly involving increased intracellular Ca 2 ⁺ levels and direct mitochondrial damage. These findings underscore the complex interplay between mitochondrial dysfunction, calcium dysregulation, and cell death pathways, highlighting the central role of mitochondria in the cytotoxicity of 2C-I and 25I-NBOMe. • 25I-NBOMe is more cytotoxic than 2C-I, likely due to its higher lipophilicity. • Both drugs induce mitochondrial dysfunction, depicted by decreased ATP levels and ΔΨm loss. • 2C-I induces autophagy and caspase-3 activation. • 25I-NBOMe triggers a rapid Ca 2 ⁺ increase. • Apoptosis was identified as a mechanism of cell death induced by both drugs.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The role of mitochondrial dysfunction and calcium dysregulation in 2C-I and 25I-NBOMe-induced neurotoxicity
- Date Crossref
- 01/04/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Universidade do Porto pays non établi dans la noticeUniversité ou école supérieure
-
Fernando Pessoa University pays non établi dans la noticeUniversité ou école supérieure
-
Cooperativa de Ensino Superior Politécnico e Universitário pays non établi dans la noticeUniversité ou école supérieure
-
Unidade de Investigação em Toxicologia & Uma Só Saúde pays non établi dans la noticeUniversité ou école supérieure
-
Faculty of Pharmacy Associate Laboratory i4HB-Institute for Health and Bioeconomy pays non établi dans la noticeUniversité ou école supérieure
-
Faculty of Sciences CIQUP-IMS/Department of Chemistry and Biochemistry pays non établi dans la noticeUniversité ou école supérieure
-
University Institute of Health Sciences-CESPU Associate Laboratory i4HB-Institute for Health and Bioeconomy pays non établi dans la noticeUniversité ou école supérieure
Universidade do Porto, Fernando Pessoa University et Cooperativa de Ensino Superior Politécnico e Universitário, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.