Neuro-modulatory Potency of Sinapic Acid in Tramadol Hydrochloride Excessive Exposure Induced Anxiety-like Behavior, Neuro-Inflammatory Cytokine, Oxidative and Morphological Damage in the Pre-frontal Cortex in Rats’ Model

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Date
2025-04
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Ms. M. B. Mondal
Abstract
Tramadol hydrochloride (TRM) is widely used for pain management, but chronic exposure can lead to neurotoxicity. Sinapic acid (SA) has been reported to be a potent antioxidant. This study investigates the impacts of SA against TRM-induced oxidative and morphological damage in the pre-frontal cortex. Thirty male Sprague Dawley rats were randomized into five groups of six (n=6) rats. Group A control received 1 ml normal saline, group B received 50 mg /kg body weight (bwt) TRM, group C received 40 mg/kg bwt SA, group D received 50 mg /kg bwt TRM and 40 mg/kg bwt SA and group E received 40 mg/kg bwt SA and 50 mg /kg bwt TRM intraperitoneally (i.p) for 30 days. Parameters tested include spatial working memory, anxiety-like behavior, malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), 8-Hydroxydeoxyguanosine (8-OHdG), Glutathione-S-transferase (GST), glutathione reductase (GR), Gama amino Butyric Acid (GABA), Brain-derived neurotrophic factor (BDNF), serotonin (5-HT), dopamine (DA), Nuclear-related factor 2 (Nrf2), interleukin-6 (IL-6), interleukin-1 (IL-1), total antioxidant capacity (TAC), total oxidant capacity (TOC), Acetylcholinesterase (AChE), glycogen (GL), Cholesterol (CL), total proteins (TP) and histology. TRM increases brain MDA, 8OHdG, TOC, IL-1, and IL-6 and decreases GST, GR, SOD, CAT, TAC, Nrf2, brain parameters (AChE, 5-TH, DA, and GABA), and BDNF. TRM exhibited neuronal degeneration. The SA significant reversal in the levels of these biomarkers and protected brain tissue from TRM-induced histopathological changes. The SA ameliorates spatial working memory and anxiety-like behavioral deficits. Therefore these findings support the potential therapeutic use of SA in mitigating behavioral and biochemical impairment associated with chronic TRM exposure.
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Keywords
Sinapic acid, tramadol hydrochloride, inflammation, oxidative stress, spatial working memory
Citation
Adelakun SA, Siyanbade JA, Adelusi KP, Kaka OZ, Ogungbe LG.. Effect of Alkaloid-rich Fraction of Dacryodes edulis Leaves on the Microstructure of the Hippocampus and Blood Glucose Levels of STZ-Induced Diabetic Wistar Rats . International Neuropsychiatric Disease Journal. 2025 Apr; 22(2): 43-65