Histological changes of the albino rat cerebellar cortex under the effect of different doses of tramadol administration

Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

“…Our results were similar to that previously reported by many authors in the rat cerebral and cerebellar cortex following chronic tramadol administration. [23][24][25] Our described structural changes reflect neuronal damage and different stages of neuronal death. Alongside, it was previously reported that the long term use of opioids causes cell apoptosis with cytoplasmic contraction, reduction in cell volume, chromatin condensation and induces neuronal damage through affection on their cytoskeleton.…”

“…40 Similar ultrastructural alterations were observed in the cerebral and cerebellar cortex of tramadol treated rats. 24,25,41 The observed mitochondrial alterations in this study might be related to oxidative and ER stress. Mitochondria are highly vulnerable to oxidative damage which causes alteration in its permeability and structure.…”

“…27 Similarly, dilated cortical vessels with RBCs extravasation and congestion of submeningeal vessels were previously documented following long term intake of tramadol. [23][24][25][26][27][28] High oxygen consumption, increased polyunsaturated fatty acids, and low antioxidants level render the brain tissue highly susceptible to oxidative stress. 29 MDA is the most abundant metabolite of free radical-induced lipid peroxidation cascade in biological systems and is commonly used as a marker for oxidative stress.…”

Complex Partial Seizure and Hippocampus Atrophy Caused by Tramadol Abuse: A Case Study

“…Another explanation is that there are evidences about association of tramadol with disorganization of neurons, apoptosis, chromatin changes, blurred nucleolus, intercellular edema, and capillary congestion in brain tissues. Tramadol also increases oxidative stress and cell damages with decreased non-enzymatic anti-oxidative activity, reduced glutathione peroxidase activity, altered glucose metabolism, and suppressed insulin signaling (10)(11)(12).…”

Impacts of morphine addiction on spermatogenesis in rats

“…They indicated that testicular function had decreased in opioid addiction ( 26 ). Some other studies evaluated the effect of opioids on other organs, the most important on cerebellar structure, and found these compounds increase the neurotoxic factors and seems to disrupt the main neural tract ( 27 ). In the literature, multiple cases of toxicity and abuse of opioid like morphine and tramadol have been reported, and they figured out these drugs effect on reproductive dysfunction, our findings are in line with recent studies carried out by El Sawy et al and El-Ghawet et al who reported that injections of tramadol would face with disorganization of seminiferous tubules with almost missing of fertility and comparatively decreased spermatogenic cells in rats ( 28 ).…”