Mixtures of environmental pharmaceuticals in marine organisms: Mechanistic evidence of carbamazepine and valsartan effects on Mytilus galloprovincialis.
Antagonistic effects
Bioaccumulation
Drug-drug interactions
Emerging contaminants
Risk assessment
Journal
The Science of the total environment
ISSN: 1879-1026
Titre abrégé: Sci Total Environ
Pays: Netherlands
ID NLM: 0330500
Informations de publication
Date de publication:
20 Feb 2023
20 Feb 2023
Historique:
received:
17
09
2022
revised:
12
11
2022
accepted:
20
11
2022
pubmed:
26
11
2022
medline:
17
1
2023
entrez:
25
11
2022
Statut:
ppublish
Résumé
Unravelling the adverse outcomes of pharmaceuticals mixture represents a research priority to characterize the risk for marine ecosystems. The present study investigated, for the first time, the interactions between two of the most largely detected pharmaceuticals in marine species: carbamazepine (CBZ) and valsartan (VAL), elucidating mechanisms that can modulate bioaccumulation, excretion and the onset of toxicity. Mytilus galloprovincialis were exposed to environmental levels of CBZ and VAL dosed alone or in combination: measurement of drug bioaccumulation was integrated with changes in the whole transcriptome and responsiveness of various biochemical and cellular biomarkers. Interactive and competing mechanisms between tested drugs were revealed by the much higher CBZ accumulation in mussels exposed to this compound alone, while an opposite trend was observed for VAL. A complex network of responses was observed as variations of gene expression, functional effects on neurotransmission, cell cycle, immune responses and redox homeostasis. The elaboration of results through a quantitative Weight of Evidence model summarized a greater biological reactivity of CBZ compared to VAL and antagonistic interactions between these compounds, resulting in a reduced effect of the antiepileptic when combined with valsartan. Overall, new perspectives are highlighted for a more comprehensive risk assessment of environmental mixtures of pharmaceuticals.
Identifiants
pubmed: 36427727
pii: S0048-9697(22)07567-2
doi: 10.1016/j.scitotenv.2022.160465
pii:
doi:
Substances chimiques
Carbamazepine
33CM23913M
Pharmaceutical Preparations
0
Water Pollutants, Chemical
0
Valsartan
80M03YXJ7I
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
160465Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors (Marica Mezzelani, Luca Peruzza, Giuseppe d'Errico, Massimo Milan, Stefania Gorbi and Francesco Regoli) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.