Hematological Impacts of Gallic Acid, Disulfiram, and Dexamethasone in a Rat Model of Lipopolysaccharide-induced Sepsis

Background: Sepsis is a life-threatening inflammatory condition associated with severe hematological disturbances.Objectives: This study evaluated the protective effects of dexamethasone (DEX), disulfiram (DSF), and gallic acid (GA) against lipopolysaccharide (LPS)-induced sepsis in rats.Methods: Thirty male Wistar rats (۱۸۰-۲۰۰ g) were divided into six groups (n=۵): a control group; an LPS (۱۰ mg/kg) group receiving a single intraperitoneal (i.p.) injection; and four pretreatment groups. The pretreatment groups received either DEX (۱ mg/kg/day, intraperitoneally (i.p), for ۲ days), GA (۲۰۰ mg/kg/day, orally, for ۷ days), DSF (۵۰ mg/kg/day, orally, for ۳ days), or a combination of GA+DSF (۲۰۰+۵۰ mg/kg/day, orally, for ۷ and ۳ days, respectively). Three hours after of the last dose in pretreatment groups, LPS was administered, and blood samples were collected ۲۰ hours post-LPS injection for hematological analysis. Results: Administration of LPS caused significant hematological changes, including: leukopenia (mean difference: −۴.۹۹×۱۰³/μL, P=۰.۰۰۲), neutrophilia (+۶.۳۱×۱۰³/μL, P<۰.۰۰۰۱), lymphopenia (−۹×۱۰³/μL, P<۰.۰۰۰۱), thrombocytopenia (−۷۰۲.۸×۱۰³/μL, P<۰.۰۰۰۱), and a highly significant increase in the neutrophil-to-lymphocyte (N/L) ratio (+۱۰.۲, ۱۰۷ folds, P=۰.۰۰۱). LPS also significantly increased the red blood cell (RBC) count (+۰.۹۱۴×۱۰۶/μL, P=۰.۰۰۶۳), hemoglobin (Hb) concentration (+۲.۰۴ g/dL, P=۰.۰۰۲۹), and hematocrit (HCT) levels (+۹.۰۲%, P=۰.۰۰۰۴). DEX significantly ameliorated the LPS-induced leukopenia and thrombocytopenia (P≤۰.۰۰۰۱) but exacerbated neutrophilia (P≤۰.۰۰۰۱) and the N/L ratio (P≤۰.۰۵). DSF reduced the LPS-induced changes in RBC count and Hb and HCT levels (P≤۰.۰۰۱–۰.۰۰۰۱) but had minimal effects on thrombocytopenia. GA showed limited influence on the LPS-induced hematological changes but modulated HCT levels (P≤۰.۰۱). The DSF-GA combination significantly decreased the LPS-induced changes in Hb and HCT levels and the N/L (P≤۰.۰۵). Moreover, DSF and GA, both alone and in combination, demonstrated a significant reduction in RBC count, neutrophils levels, the N/L ratio, and HCT levels (P<۰.۰۵-۰.۰۰۰۱) compared with DEX. Conclusion: The DSF+GA combination demonstrated good efficacy in mitigating sepsis-induced hematological disruptions compared to DEX by targeting inflammation through distinct mechanisms, offering a novel therapeutic approach in the management of sepsis.

کلیدواژه ها:

Disulfiram (DSF) ، Gallic acid (GA) ، Hematology ، Neutrophil-to-lymphocyte (N/L) ratio ، sepsis