Assessments of Neuro-protective and Antioxidant Activities of Curcuma longa (Linn) and Zingiber officinale (Roscoe)-Supplemented Feed in Tramadol-exposed Male Wistar Rats

Aim: This study aimed to investigate the protective effects of Zingiber officinale Roscoe (ginger) and Curcuma longa Linn(turmeric) on tramadol-induced neurotoxicity.

Study Design: Twenty male Wistar rats, with an average weight of 130 g, were randomly divided into four groups (n=5 per group). Group 1 served as the control and was fed normal feed, Group 2 received tramadol hydrochloride at a dose of 25mg/kg body weight and fed normal feed while Groups 3 and 4 were treated with tramadol and fed Z. officinale and C. longa (10% w/w supplemented feed) respectively. Treatments were administered daily for 90 days.

Place and Duration of Study: The study was conducted in the Laboratory of the Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, from March 2022 to January 2023.

Methodology: At the end of the treatment period, animals were sacrificed by cervical dislocation and blood samples were collected via cardiac puncture. The brains were harvested for biochemical assays and histological analysis. Superoxide dismutase (SOD) activity, reduced glutathione (GSH), and malondialdehyde (MDA) concentrations were determined by spectrophotometry, while nitric oxide concentration was measured using a colourimetric method. Additionally, the levels of 8-hydroxyl deoxyguanosine (8-OHdG) and dopamine were quantified by ELISA, and monoamine oxidase (MAO), gamma-aminobutyric acid (GABA), and acetylcholinesterase (AChE) activities were measured spectrophotometrically. Histological examination of the brain tissue was conducted using Hematoxylin and Eosin (H&E) staining. Data were subjected to one-way analysis of variance (ANOVA) using GraphPad Prism 5 statistical software to compare the difference among the groups.

Results: The results indicated a significant decrease (P<0.5) in SOD activity (.69±.037 to .37±0.51 U/mol) and GSH concentration (.76±.029 to .29±.035 mM), coupled with a significant increase (P<0.5) in levels of MDA (29.24±.60 to 57.23±1.64 µM), nitric oxide (from 8.25±.47 to 16.25±.75 µM), 8-OHdG (9.20±.37 to 14.47±.61 ng/ml), dopamine (55.74±0.57 to 72.90±2.94 pg/ml), MAO (1.59±0.02 to 4.90±0.27 U/g protein), and AChE (.29±0.04 to 1.50±0.29 U/ml) activities in the tramadol-treated group compared to the control group. Additionally, there was a significant depletion in GABA levels (73.90±2.54 to 40.13±1.51 pg/ml) in the tramadol group. Histological analysis revealed degenerative changes in the neurons of tramadol-treated rats. However, supplementation of feed with Z. officinale and C. longa significantly prevented these damaging biochemical changes, preserving neuronal structure and function.

Conclusion: The study demonstrated that Z. officinale and C. longa offer neuroprotection against tramadol toxicity by preserving key neural biochemistry involving acetylcholine esterase, monoamine oxidase, dopamine and gamma-aminobutyric acid via potent antioxidant properties. These findings suggest potential therapeutic benefits of these natural supplements in mitigating the adverse effects of tramadol on the brain.