Evaluation of antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture

Abstract

Background: One of the main reasons of failure in surgical treatment of primary acquired nasolacrimal duct obstruction is excessive postoperative scarring of the dacryostomy. Despite the variety of procedures designed to prevent this, conflicting evidence of their efficacy and safety provide incentive for further research of antifibrotic therapeutics for adjunctive use in dacryocystorhinostomy.Aims: To evaluate the antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture.Materials and methods: Human nasal mucosal fibroblast cell cultures were established using samples obtained from 3 consecutive patients undergoing endonasal endoscopic dacryocystorhinostomy. Cell viability following treatment with pirfenidone was evaluated using MTS-assay. Induced inhibition of cell proliferation and migration was determined using scratch wound assay.Results: In this study pirfenidone exhibited a significant dose-dependent inhibiting effect on fibroblast proliferation with insignificant cell toxicity. Cell viability following 48 hours of incubation with various pirfenidone concentrations did not drop below 80%. The recovery of the fibroblast monolayer assessed after 24 hours of incubation was 84.88 and 8.26% in the control group, at a drug concentration of 0.15 mg/ml. Cell proliferation and migration was severely inhibited in cell culture specimens treated with pirfenidone compared to controls. The difference between groups was statistically significant (p=0,001).Conclusions: In our study pirfenidone demonstrated a pronounced antifibrotic effect. It is unlikely that inhibition of proliferation and migration of human nasal mucosal fibroblasts is mediated by cell toxicity of this medication as it was evaluated as low. Nonetheless an in vitro analysis is insufficient to judge pirfenidone’s efficacy and safety in preventing cicatrix formation following dacrycystorhinostomy.