University of Tehran Iranian Journal of Veterinary Medicine 2251-8894 20 3 2026 07 01 Hematological Impacts of Gallic Acid, Disulfiram, and Dexamethasone in a Rat Model of Lipopolysaccharide-induced Sepsis 529 536 103104 10.32598/ijvm.20.3.1005787 EN Zahra Hojati Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Ali Rassouli Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Farhang Sasani Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Jamileh Salar Amoli Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Hamidreza Javadi Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. 0000-0003-3465-3854 Journal Article 2025 04 28 <strong>Background</strong>: Sepsis is a life-threatening inflammatory condition associated with severe hematological disturbances.<br /><strong>Objectives</strong>: This study evaluated the protective effects of dexamethasone (DEX), disulfiram (DSF), and gallic acid (GA) against lipopolysaccharide (LPS)-induced sepsis in rats.<br /><strong>Methods</strong>: Thirty male Wistar rats (180-200 g) were divided into six groups (n=5): a control group; an LPS (10 mg/kg) group receiving a single intraperitoneal (i.p.) injection; and four pretreatment groups. The pretreatment groups received either DEX (1 mg/kg/day, intraperitoneally (i.p), for 2 days), GA (200 mg/kg/day, orally, for 7 days), DSF (50 mg/kg/day, orally, for 3 days), or a combination of GA+DSF (200+50 mg/kg/day, orally, for 7 and 3 days, respectively). Three hours after of the last dose in pretreatment groups, LPS was administered, and blood samples were collected 20 hours post-LPS injection for hematological analysis. <br /><strong>Results</strong>: Administration of LPS caused significant hematological changes, including: leukopenia (mean difference: −4.99×10³/μL, P=0.002), neutrophilia (+6.31×10³/μL, P<0.0001), lymphopenia (−9×10³/μL, P<0.0001), thrombocytopenia (−702.8×10³/μL, P<0.0001), and a highly significant increase in the neutrophil-to-lymphocyte (N/L) ratio (+10.2, 107 folds, P=0.001). LPS also significantly increased the red blood cell (RBC) count (+0.914×106/μL, P=0.0063), hemoglobin (Hb) concentration (+2.04 g/dL, P=0.0029), and hematocrit (HCT) levels (+9.02%, P=0.0004). DEX significantly ameliorated the LPS-induced leukopenia and thrombocytopenia (P≤0.0001) but exacerbated neutrophilia (P≤0.0001) and the N/L ratio (P≤0.05). DSF reduced the LPS-induced changes in RBC count and Hb and HCT levels (P≤0.001–0.0001) but had minimal effects on thrombocytopenia. GA showed limited influence on the LPS-induced hematological changes but modulated HCT levels (P≤0.01). The DSF-GA combination significantly decreased the LPS-induced changes in Hb and HCT levels and the N/L (P≤0.05). 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<0.05-0.0001) compared with DEX. <br /><strong>Conclusion</strong>: 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. https://ijvm.ut.ac.ir/article_103104_ff094932e95b8c5b41cee4c2edc9032a.pdf