Biochemical and Histopathological Alterations Induced by Tramadol.

Abstract

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.