Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat's striatum: An in vitro- in vivo approach.
Neurodegeneration
Neuroinflammatory
Striatum
Tramadol
Journal
Journal of chemical neuroanatomy
ISSN: 1873-6300
Titre abrégé: J Chem Neuroanat
Pays: Netherlands
ID NLM: 8902615
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
10
04
2020
revised:
31
05
2020
accepted:
01
06
2020
pubmed:
12
6
2020
medline:
16
6
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. It bears several side effects including emotional instability and anxiety. In this study, we focused on the alteration in expression of autophagic and apoptotic genes in PC-12 cells for our in vitro and structural and functional changes of striatum for our in vivo under chronic exposure of tramadol. For in vitro side of the study, PC12 cells were exposed to tramadol (50 μM) and expression of apoptosis and autophagy genes were determined. In parallel, rats were daily treated with tramadol at doses of 50 mg/kg for three weeks for the in vivo side. Motor coordination, EMG, histopathology and gene expression were done. Our in vitro findings revealed that tramadol increased expression of apoptosis and autophagy genes in PC12 cells. Moreover, our in vivo results disclosed that tramadol not only provoked atrophy of rats' striatum, but also triggered microgliosis along with neuronal death in the striatum. Tramadol also reduced motor coordination and muscular activity. Altogether, our data indicated that tramadol induced neurotoxicity in the PC12 cells via apoptosis and autophagy and in striatum chiefly through activation of neuroinflammatory and apoptotic responses.
Sections du résumé
AIM AND BACKGROUND
Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. It bears several side effects including emotional instability and anxiety. In this study, we focused on the alteration in expression of autophagic and apoptotic genes in PC-12 cells for our in vitro and structural and functional changes of striatum for our in vivo under chronic exposure of tramadol.
METHODS
For in vitro side of the study, PC12 cells were exposed to tramadol (50 μM) and expression of apoptosis and autophagy genes were determined. In parallel, rats were daily treated with tramadol at doses of 50 mg/kg for three weeks for the in vivo side. Motor coordination, EMG, histopathology and gene expression were done.
RESULTS
Our in vitro findings revealed that tramadol increased expression of apoptosis and autophagy genes in PC12 cells. Moreover, our in vivo results disclosed that tramadol not only provoked atrophy of rats' striatum, but also triggered microgliosis along with neuronal death in the striatum. Tramadol also reduced motor coordination and muscular activity.
CONCLUSION
Altogether, our data indicated that tramadol induced neurotoxicity in the PC12 cells via apoptosis and autophagy and in striatum chiefly through activation of neuroinflammatory and apoptotic responses.
Identifiants
pubmed: 32526246
pii: S0891-0618(20)30089-2
doi: 10.1016/j.jchemneu.2020.101820
pii:
doi:
Substances chimiques
Analgesics, Opioid
0
Tramadol
39J1LGJ30J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101820Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.