Fraxin in Combination with Dexamethasone Attenuates LPS-Induced Liver and Heart Injury and Their Anticytokine Activity in Mice

Background. Cytokine storm syndrome (CSS) is a major cause of morbidity and mortality in people suffering from hyperinflammatory status, which diverse etiological factors, including pathogens, therapeutic interventions, malignancies, and autoimmune disorders, can instigate. Since there is limited research on the antioxidant properties of fraxin and no studies have investigated its potential as an anticytokine storm agent, it is important to note that most studies have primarily focused on proinflammatory cytokines such as IL-1β, IL-6, and TNFα during cytokine storm. However, little research discusses the role of chemokines, particularly IL-8, during cytokine storms. Therefore, further investigation is warranted into the role of fraxin as an anticytokine storm agent and the involvement of IL-8 in cytokine storms. The present study examines the preventive efficacy of fraxin and the combination of fraxin and dexamethasone (FD) in mitigating lipopolysaccharide-induced systemic inflammation in mice caused by Escherichia coli, 055: B5. Methods. Five groups of ten mice were randomly assigned: LPS only group (5 mg/kg, intraperitoneally i.p.), control (normal saline N.S. 1 ml/kg, i.p.), concentrations were selected based on previous literature, fraxin (120 mg/kg, i.p.), dexamethasone (5 mg/kg, i.p.), fraxin + dexamethasone (FD) (60 mg/kg + 2.5 mg/kg, i.p.), administered one hour before LPS injection (5 mg/kg,i.p.), animals were euthanized next day, and interleukin-8 (IL-8) was quantified in serum using an enzyme-linked immunosorbent assay. The liver and heart tissues underwent histopathological analysis to assess morphological changes. For data analysis using ANOVA and Tukey post hoc tests, the Kruskal–Wallis and Mann–Whitney U tests were employed to analyze the histological results. Results. A significant decline in IL-8 levels was recorded in the treatment groups almost to the same degree (p