Macroscopic and microscopic evaluation of the therapeutic effects of fosfomycin on surgical wound healing in a rat model.

Abstract

This study evaluated the therapeutic potential of fosfomycin on surgical wound healing in a sterile rat model, emphasizing its immunomodulatory and regenerative effects beyond antimicrobial activity. Thirty male Sprague Dawley rats were randomly assigned to five groups: negative control, positive control (dexamethasone 1 mg/kg), and three fosfomycin-treated groups (75, 150, and 300 mg/kg, intraperitoneally). A standardized full-thickness dorsal wound was surgically induced, and treatments were administered over a 14-day period. Macroscopic healing was assessed using a validated Wound Healing Score (WHS) on days 1, 3, 5, 7, 9, 12, and 14. Histological analyses using H&E and Masson's trichrome staining were performed on days 7 and 14. Additionally, ELISA was used to quantify pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-10) and VEGF levels, while western blotting assessed the expression of NF-κB, p-NF-κB, NLRP3, and caspase-3 proteins. Fosfomycin at 150 mg/kg significantly accelerated wound closure, enhanced collagen deposition, improved re-epithelialization, and increased neovascularization compared to control groups. ELISA results showed reduced TNF-α and IL-6 levels and elevated IL-10 and VEGF levels, indicating an anti-inflammatory and a pro-angiogenic profile. Western blot analyses confirmed the downregulation of NF-κB, p-NF-κB, caspase-3, and NLRP3, suggesting suppressed inflammatory signaling and apoptosis. These results support the hypothesis that fosfomycin facilitates wound healing through modulation of immune responses and tissue regeneration pathways. 150 mg/kg dose emerged as the most effective, highlighting a potential therapeutic window. Collectively, the findings suggest that fosfomycin may serve as a dual-function agent in surgical wound care, warranting further investigations in clinical and infected wound models.