Document Type : Original Articles
Authors
1
Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
2
Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
3
Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
10.32598/ijvm.20.3.1005787
Abstract
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 (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.
Results: 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.
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.
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