Targeted Anti-Inflammatory Effects of Chloramphenicol via TLR4 Inhibition in Postoperative Hemorrhoid Treatment: A Clinico-Computational Cohort Study.

Abstract

Introduction: Postoperative hemorrhoidectomy wounds are prone to inflammation and microbial infection due to their anatomical location, necessitating effective therapeutic strategies. Chloramphenicol (CHL) is a broad-spectrum antibiotic with potential anti-inflammatory properties via Toll-like receptor 4 (TLR4) inhibition. This clinico- computational cohort study investigates CHL's dual therapeutic mechanism in postoperative hemorrhoid management, combining clinical outcomes with molecular modeling to elucidate its anti-inflammatory and antimicrobial effects.

Methods: A prospective, controlled cohort study was conducted with 155 patients (55 CHL, 39 reference treatment [PR], 61 control) undergoing hemorrhoidectomy. CHL ointment (≤120 mg/day) was applied topically until granulation tissue appeared. Clinical outcomes, including edema resolution, granulation tissue formation, and pain scores, were assessed using ImageJ for wound area analysis and the visual analog scale (VAS) for pain. Molecular docking and dynamics simulations were performed using AutoDock and AMBER 22 to evaluate CHL's binding affinity to TLR4 compared to the reference inhibitor TAK-242. Statistical analyses included ANOVA, Mann-Whitney U tests, and post hoc power calculations.

Results: CHL significantly accelerated wound healing, with 53.2% of patients achieving complete edema resolution by day 3 (vs. 43.6% by day 4) and faster granulation tissue formation (3.58 ± 0.60 days vs. 7.08 ± 1.20 days in controls, p<0.0001). Pain scores were significantly reduced in the CHL group. Molecularly, CHL exhibited superior TLR4 binding (ΔGtot = -25.97 kcal/mol vs. -20.69 kcal/mol for TAK-242), with stable complex formation and persistent interactions at Ile-135 (buried surface area: 350 Å2). Healing times were 13.5-19.8 days faster in the CHL group (mean 41 days vs. 54.5-60.8 days in controls).

Conclusion: CHL demonstrates dual therapeutic potential in postoperative hemorrhoid management by inhibiting TLR4-mediated inflammation and microbial infection. Its superior binding affinity and clinical efficacy suggest it as a promising multifunctional agent. Further in vitro and long-term studies are needed to validate these findings and explore broader applications in surgical wound care.