Effects of Pirfenidone on Peripheral Nerve Healing in an Experimental Sciatic Nerve Injury Model in Rats

Introduction: Pirfenidone is a molecule that has recently been tested in extrapulmonary diseases owing to its notable anti-inflammatory and antioxidative mechanisms of action, in addition to its antifibrotic characteristics.The objective of this investigation was to elucidate the impact of pirfenidone administration on the restorative processes in a rat model subjected to peripheral nerve injury.Methods: In the present investigation, 32 rats were randomly allocated into four groups (n=8 per group).A standardized crush injury was induced in the right sciatic nerve by applying an aneurysm clip for five minutes in two groups, one of which received pirfenidone.A 10-mm sciatic nerve segment encompassing the injury site was harvested for histopathological evaluation.On days 15 and 30, the sciatic functional index (SFI) was calculated.Histopathological evaluation included injury grading, axon count, and immunohistochemical staining for Caspase-3 and nuclear factor kappa B (NF-κB).Results: On day 15, no statistically significant difference was observed between the Injury + Pirfenidone and Injury groups in SFI values (p=0.086).However, by day 30, SFI values were significantly higher in the Injury + Pirfenidone group than in the Injury group (p<0.001).Caspase-3 and NF-κB immunoreactivity was numerically lower in the Injury + Pirfenidone group, but neither difference reached statistical significance (p=0.195 and p=0.161, respectively).Conclusion: Pirfenidone treatment was associated with improved functional recovery at day 30 following experimental sciatic nerve injury.Although Caspase-3 and NF-κB immunoreactivity was numerically lower in the pirfenidone-treated group, these differences were not statistically significant and therefore do not establish an anti-apoptotic or anti-inflammatory mechanism.Further studies are needed to clarify the mechanisms underlying the observed functional improvement.