Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats.
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.
['Mohamed|Hanaa M|HM|', 'Mahmoud|Ayman M|AM|']
D000701:Analgesics, Opioid D000818:Animals D017209:Apoptosis D015306:Biogenic Monoamines D002540:Cerebral Cortex D004305:Dose-Response Relationship, Drug D004334:Drug Administration Schedule D007249:Inflammation D018836:Inflammation Mediators D008297:Male D018377:Neurotransmitter Agents D018384:Oxidative Stress D011897:Random Allocation D051381:Rats D014147:Tramadol
Tramadol Inflammation Apoptosis 8-Oxo-dG ROS