The Anti-nociceptive Effect of Ellagic Acid in Streptozotocin-induced Hyperglycemic Rats by Oxidative Stress Involvement.

Introduction: Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats. Methods: Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated. Results: Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats. Conclusion: These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception. Highlights: Hyperalgesia is among the current complications of diabetes mellitus.Oxidative stress and inflammation were influential in its development.EA has some biological activities, including antioxidant and anti-inflammatory effects. Plain Language Summary: DN is among the most common chronic complications of diabetes among diabetic patients. DPN is mainly characterized by pain perception alterations, increased sensitivity to mild painful stimuli (hyperalgesia), and abnormal pain sensitivity to stimuli. On the other hand, hyperglycemia by induction of multiple changes, such as fatty acid metabolism abnormalities plays a crucial role in developing DN. Oxidative stress and inflammation are involved in the pathogenesis of DPN. The lack of efficacy and various adverse effects of the current medications for DNP, therefore, new therapeutic candidates are continuously required to improve DNP. Several studies reported the antinociceptive activity of EA in different animal models of pain, such as formalin. Since oxidative stress is involved in diabetic hyperalgesia, compounds with antioxidant properties are good candidates for DN management. Therefore, this research aimed to determine the possible effectiveness of EA and evaluate some oxidative stress-related mechanisms.