Go to:
Logótipo
Você está em: Start > Publications > View > 4-Fluoromethamphetamine (4-FMA) induces in vitro hepatotoxicity mediated by CYP2E1, CYP2D6, and CYP3A4 metabolism
Publication

4-Fluoromethamphetamine (4-FMA) induces in vitro hepatotoxicity mediated by CYP2E1, CYP2D6, and CYP3A4 metabolism

Title
4-Fluoromethamphetamine (4-FMA) induces in vitro hepatotoxicity mediated by CYP2E1, CYP2D6, and CYP3A4 metabolism
Type
Article in International Scientific Journal
Year
2021
Authors
Bravo, RR
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Valente, MJ
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Silva, JP
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Felix Carvalho
(Author)
FFUP
View Personal Page You do not have permissions to view the institutional email. Search for Participant Publications View Authenticus page Without ORCID
Bastos, MD
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
da Silva, DD
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Journal
Title: ToxicologyImported from Authenticus Search for Journal Publications
Vol. 463
ISSN: 0300-483X
Publisher: Elsevier
Indexing
Publicação em ISI Web of Knowledge ISI Web of Knowledge - 0 Citations
Publicação em Scopus Scopus - 0 Citations
Other information
Authenticus ID: P-00V-MB7
Abstract (EN): 4-Fluoromethamphetamine (4-FMA) is an amphetamine-like psychoactive substance with recognized entactogenic and stimulant effects, but hitherto unclear toxicological mechanisms. Taking into consideration that the vast majority of 4-FMA users consume this substance through oral route, the liver is expected to be highly exposed. The aim of this work was to determine the hepatotoxic potential of 4-FMA using in vitro hepatocellular models: primary rat hepatocytes (PRH), human hepatoma cell lines HepaRG and HepG2, and resorting to concentrations ranging from 37 mu M to 30 mM, during a 24-h exposure. EC50 values, estimated from the MTT viability assay data, were 2.21 mM, 5.59 mM and 9.57 mM, for each model, respectively. The most sensitive model, PRH, was then co-exposed to 4-FMA and cytochrome P450 (CYP) inhibitors to investigate the influence of metabolism on the toxicity of 4-FMA. Results show that CYP2E1, CYP3A4 and CYP2D6 have major roles in 4-FMA cytotoxicity. Inhibition of CYP2D6 and CYP3A4 led to left-geared shifts in the concentration-response curves of 4-FMA, hinting at a role of these metabolic enzymes for detoxifying 4-FMA, while CYP2E1 inhibition pointed towards a toxifying role of this enzyme in 4-FMA metabolism at physiologically-relevant concentrations. The drug also destabilised mitochondrial membrane potential and decreased ATP levels, increased the production of reactive oxygen and nitrogen species and compromised thiol antioxidant defences. 4-FMA further affected PRH integrity by interfering with the machinery of apoptosis and necrosis, increasing the activity of initiator and effector caspases, and causing loss of cell membrane integrity. Potential for autophagy was also observed. This research contributes to the growing body of evidence regarding the toxicity of new psychoactive substances, in particular regarding their hepatotoxic effects; the apparent influence of metabolism over the resulting cytotoxicity of 4-FMA shows that there is a substantial degree of unpredictability of the consequences for users that could be independent of the dose.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 11
Documents
We could not find any documents associated to the publication.
Related Publications

Of the same authors

From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC (2021)
Article in International Scientific Journal
Bravo, RR; Helena Carmo; Valente, MJ; Silva, JP; Felix Carvalho; Bastos, MD; da Silva, DD

Of the same journal

The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine (2004)
Article in International Scientific Journal
Carvalho, M; Remiao, F; Milhazes, N; Borges, F; Fernandes, E; Carvalho, F; Bastos, ML
The synthetic cannabinoid WIN-55,212 induced-apoptosis in cytotrophoblasts cells by a mechanism dependent on CB1 receptor (2017)
Article in International Scientific Journal
Almada, M; Costa, L; Fonseca, BM; Amaral, C; Teixeira, NA; Georgina Correia da Silva
The psychoactive compound of Cannabis sativa, Delta(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover (2015)
Article in International Scientific Journal
Costa, MA; Fonseca, BM; Franklim Marques; Teixeira, NA; Georgina Correia da Silva
The age factor for mitoxantrone's cardiotoxicity: Multiple doses render the adult mouse heart more susceptible to injury (2015)
Article in International Scientific Journal
Jose Luis Dores Sousa; Jose Alberto Duarte; Vitor Seabra; Maria de Lourdes Bastos; Felix Carvalho; Vera Marisa Costa
Synthetic cannabinoids and endometrial stromal cell fate: Dissimilar effects of JWH-122, UR-144 and WIN55,212-2 (2019)
Article in International Scientific Journal
Fonseca, BM; Fernandes, R; Almada, M; Santos, M; Felix Carvalho; Teixeira, NA; Georgina Correia da Silva

See all (42)

Recommend this page Top
Copyright 1996-2024 © Faculdade de Farmácia da Universidade do Porto  I Terms and Conditions  I Acessibility  I Index A-Z  I Guest Book
Page created on: 2024-04-23 at 05:56:04 | Acceptable Use Policy | Data Protection Policy | Complaint Portal