Amantadine Mitigates LPS-Induced Pancreatic Inflammation via Suppression of IFN-β, IL-1β, and TNF-α Expressions in Rat Islet

Abstract

Lipopolysaccharide (LPS)-induced systemic inflammation is known to impair pancreatic tissue integrity, particularly targeting β-cells within the islets of Langerhans, through cytokine-mediated injury. The research examined how amantadine (AMA) as an NMDA receptor antagonist protects against LPS-induced pancreatic damage in rats through histopathological and immunohistochemical assessments. The study involved thirty-two adult female Wistar albino rats weighing between 250–300 g which were randomly assigned to four groups (n=8): Control, LPS (5 mg/kg, i.p.), LPS+AMA (45 mg/kg, i.p.), and AMA-only. The rats received LPS administration followed by sacrifice under anesthesia six hours later. Pancreatic tissues were harvested for histopathological and immunohistochemical evaluations. Hematoxylin–eosin staining was used to assess edema, hyperemia, infiltration, and degeneration. Immunohistochemical analysis was performed to detect IFN-β, IL-1β, and TNF-α expressions in the islets of Langerhans. LPS administration resulted in significant histopathological injury, including interstitial edema, vascular congestion, inflammatory infiltration, and β-cell degeneration in the islets. Immunohistochemistry revealed a marked increase in IFN-β, IL-1β, and TNF-α expressions in the LPS group. Following AMA treatment both histopathological scores and cytokine expressions significantly mitigated compared to the LPS group (p < 0.001 for all). The control and AMA-alone groups maintained minimal expression of cytokine and normal pancreatic histology. LPS-induced pancreatic injury diminished via AMA treatment by suppressing inflammatory cytokine expression and preserving islet architecture. These findings suggest that AMA may have therapeutic potential in managing endotoxin-induced pancreatic dysfunction.

Keywords

• Amantadine
• Lipopolysaccharide
• Pancreatic inflammation
• Islets of Langerhans
• Immunohistochemistry

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