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
Sunday Aderemi Adelakun *
Department of Human Anatomy, Federal University of Technology, Akure, Nigeria.
Jacob Adewale Siyanbade
Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Kehinde Precious Adelusi
Department of Human Anatomy, Federal University of Technology, Akure, Nigeria.
Opeyemi Zainab Kaka
Department of Human Anatomy, Federal University of Technology, Akure, Nigeria.
Luke Gbenga Ogungbe
Department of Anatomy, Lead City University, Ibadan, Nigeria.
*Author to whom correspondence should be addressed.
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.
Keywords: Sinapic acid, tramadol hydrochloride, inflammation, oxidative stress, spatial working memory