Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats - 06/01/19
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Graphical abstract |
Highlights |
• | Tramadol activates NF-κB and up-regulates iNOS and cytokines. |
• | Tramadol induces oxidative DNA damage in the cerebrum. |
• | Tramadol up-regulates cerebral p53 and Bax, and down-regulates Bcl-2. |
• | Tramadol increases cerebral serotonin and catecholamines. |
Abstract |
Tramadol is an opioid used as analgesic for treating moderate or sever pain. The long-term use of tramadol can induce several deleterious effects. We investigated the impact of chronic tramadol administration on the cerebrum of rats, focusing on oxidative damage, inflammation, apoptosis and changes in monoamine neurotransmitters. Rats received 30 or 60 mg/kg body weight tramadol dissolved in physiological saline daily for 8 weeks via oral gavage. Tramadol-induced rats showed significantly increased cerebral lipid peroxidation and nitric oxide, and deceased GSH content and activity and expression of the antioxidant enzymes. Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-α and IL-6) and expression of NF-κB, iNOS, TNF-α and IL-6 in the cerebrum of rats. Monoamine neurotransmitters, 8-oxo-7,8-dihydro-2′-deoxyguanosine, and gene and protein expression levels of p53 and Bax were significantly increased in the cerebrum of tramadol-induced rats. In contrast, chronic tramadol administration down-regulated Bcl-2 both gene and protein expression in the cerebrum of rats. In conclusion, our results indicate that the neurotoxic effect of chronic tramadol consumption is mediated via oxidative stress, inflammation and apoptosis. Tramadol provoked lipid peroxidation, up-regulated inflammation and apoptosis markers and altered neurotransmission in the cerebrum of rats.
Le texte complet de cet article est disponible en PDF.Keywords : Tramadol, ROS, Apoptosis, Inflammation, 8-Oxo-dG
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Vol 110
P. 239-247 - février 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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