Medical Journal of the Islamic Republic Of Iran

en Biochemical and Histopathological Alterations Induced by Tramadol Clinical Toxicology Clinical Toxicology Original Research Original Research     Background: Drug addiction is a serious public health concern. Tramadol addiction and dependence have been documented in recent years, most commonly in young adults, making tramadol use a significant health concern.   The study investigated the long-term effects of tramadol intoxication on the γ-aminobutyric acid (GABA) system and tricarboxylic acid cycle enzymes in the brains of rats, focusing on regions with a high number of GABAergic neurons.    Methods: In this animal study, three treatment groups of adult male rats were considered. Rats were divided into three treatment groups: control no tramadol was given, Gp 25 mg/Kg tramadol was given 25 mg/kg for one month by oral gavage, and Gp 50 mg/Kg tramadol was given 50 mg/kg for one month by oral gavage for one month, and the enzyme activities for GABA transaminase (GABA-T), succinic semialdehyde dehydrogenase (SSA-DH), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) were measured using ELISA kits, on brain tissue samples from the cerebellum, brain stem, cerebral cortex, thalamus, and hypothalamus. Histopathological analysis of the cerebral cortex was conducted using hematoxylin-eosin and Nauta silver staining. Statistical analysis for GABA shunt enzymes and tricarboxylic acid cycle enzymes was conducted using one-way ANOVA followed by Tukey’s multiple means comparisons.    Results: Tramadol significantly (P < 0.05) reduced the levels of GABA-T, SSA-DH, and IDH enzymes across various brain regions, with the most pronounced reductions observed in the brain stem and hypothalamus. In contrast, SDH enzyme levels remained largely unchanged in most regions. Additionally, structural changes in the brain were noted, including vascular congestion, neuronal degeneration, and disruption of cortical layers. These alterations were more severe in the high-dose group, suggesting that higher doses of Tramadol may lead to more extensive brain damage.    Conclusion: Tramadol exposure was found to cause biochemical and histopathological alterations in the nervous tissue through impairment of GABA metabolism.   Tramadol, Addiction, GABA metabolism, Cerebral cortex 240 247 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-8757-3&slc_lang=en&sid=1 Husam Abazid h_abazid@asu.edu.jo 200319475328460089251 200319475328460089251 No Department of Oral Surgery and Diagnostic Sciences, Faculty of Dentistry, Applied Science Private University, Amman, Jordan Nour Alabbas nour3abass@gmail.com 200319475328460089252 200319475328460089252 No Chaîne de l’Espoir Luxembourg, Amman, Jordan Alaa Hammad alaa.hammad@zuj.edu.jo 200319475328460089253 200319475328460089253 No Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan Osama I. Ramadan dr.osama784@yahoo.com 200319475328460089254 200319475328460089254 Yes Histology Department, Damietta Faculty of Medicine, Al-Azhar University, Egypt Esraa Ebraheem Al Jomaa esraagomaa8@gmail.com 200319475328460089255 200319475328460089255 No Department of Pharmacology, Faculty of Pharmacy, Health Science Institution, Mersin University, Turkey Mumen Fathi Amer m_amer@asu.edu.jo 200319475328460089256 200319475328460089256 No Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan Frank Scott Hall frank.hall@utoledo.edu 200319475328460089257 200319475328460089257 No Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA