Eugenol Ameliorates Anxiety and Oxido-Inflammatory Markers Induced by Tramadol in the Hippocampus of Wistar Rats

Tramadol, a synthetic opioid widely used for pain management, is associated with neurotoxic effects, particularly in the hippocampus, due to its ability to induce oxidative stress and inflammation. This study evaluated the effects of eugenol on tramadol-induced anxiety-like behaviour and alterations in oxidative-inflammatory markers in the hippocampus of Wistar rats. Forty Wistar rats, divided into five groups (n=8), were used for this study. Group A received feed and water ad libitum. Tramadol (50 mg/kg) was given orally for 14 days to Groups B, C, and D. While Groups C AND D were treated with 300 mg/kg and 400 mg/kg of Eugenol, respectively, after tramadol administration, Group E received 600 mg/kg of eugenol for 28 days orally. Group B was not treated with eugenol. The anxiety level of the rats was assessed using the open field test (OFT). The levels of oxidative stress, antioxidants, and pro-inflammatory cytokines were assessed using brain homogenate. There was a significant increase in the anxiety-like behaviours in tramadol-treated rats, which were significantly reduced following eugenol administration in Groups C and D. Biochemical assays showed elevated malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-3 (IL-3), alongside decreased superoxide dismutase (SOD) and catalase (CAT) in the tramadol group; these parameters were ameliorated in the eugenol-treated groups. Histological analysis demonstrated neuronal damage in the CA1 and CA3 regions of tramadol-treated Groups, which improved with eugenol treatment. These findings suggest that eugenol exerts anxiolytic, antioxidant, and anti-inflammatory effects, offering neuroprotection against tramadol-induced hippocampal damage.