Ellagic Acid Protects Spleen Injury Against E. coli Infection: Role of Hypoxia-Induced Factor-1 and Antioxidant Activities in vivo

Background and Objective: The inflammation and oxidative stress in vivo caused by Escherichia coli (E. coli) infection are of great significance and play a crucial role in the clinical diagnosis for both injury to and damage to different organs. The present study was conducted to investigate the anti-inflammatory and antioxidant properties of ellagic acid (EA) against fatal bacterial infections in vivo. Materials and Methods: Forty mice were assigned to four groups (N = 10): Group I (control), Group II (EA only, 70 mg/kg/day for 12 days), Group III (E. coli infection at 1×10 CFU/kg for 7 days) and Group IV (E. coli+EA, treated simultaneously for 12 days). On day 13, blood and spleen samples were collected to assess Pro-Inflammatory Cytokines (IL-1β, TNF-α), Inducible Nitric Oxide Synthase (iNOS), antioxidant enzymes (SOD, GST, GSH-Px), Hypoxia-Induced Factor-1 Alpha (HIF-1α) and spleen histopathology. Data were analyzed using One-way ANOVA and Tukey's post hoc test (pResults: Levels of serum Pro-inflammatory cytokines (interleukin-beta and tumor necrosis factor-alpha), inducible nitric oxide synthase, spleen antioxidant parameters and hypoxia-induced factor-1 alpha (HIF-1α) decreased in Group III after infection. The immunoreactivity of HIF-1α was noted and inspected; histopathological spleen staining showed disturbed spleen architectures with increased levels of white pulp, areas of hemorrhage, areas of necrosis and fibrosis of the trabeculae. However, biochemical markers, immunohistochemical staining and histopathological examination revealed that there were improvements in Group IV, showing the partial restoration of normal spleen architecture with no hemorrhaging and minimal necrosis and fibrosis. Conclusion: The results confirmed the ability of EA to protect against spleen damage and injury induced by E. coli via regulation of HIF-1α and reduced oxidative damage. The data analysis highlights the potential of EA as a protective agent against spleen injury and damage.