Evaluation of Pirfenidone as a Novel Radioprotectant for Radiation-induced Intestinal Injury.

BACKGROUND/AIM: The objective of this study was to investigate the radioprotective and radiomitigative effects of pirfenidone (PFD), a clinically approved drug used for the treatment of idiopathic pulmonary fibrosis, in a mouse model of radiation-induced intestinal injury.

MATERIALS AND

METHODS

Male C57BL/6J mice (8 weeks old) received oral PFD (300 mg/kg) at specified time points relative to irradiation (IR). In experiment 1, the mice were divided into an IR + PFD group (PFD administered 6 h before IR) and an IR-alone group. Mice were irradiated with a dose of 10 Gy, and duodenal tissues were harvested 4 h later and evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry for ataxia-telangiectasia mutated (ATM) and γH2AX. In experiment 2, intestinal crypt survival was assessed 3.5 days after 15-Gy IR in four groups: IR-alone; PFD administered 6 h before IR (PFD-pre); PFD administered 24 h after IR (PFD-post); and PFD administered before and after IR (PFD-pre/post).

RESULTS

The number of TUNEL-positive cells per crypt was significantly lower in the IR + PFD group than in the IR-alone group (p<0.001), with the greatest reduction at the crypt base. DNA damage response markers showed a trend toward decreased ATM and increased γH2AX expression in the IR + PFD group compared with the IR-alone group (p=0.071 and 0.077, respectively). Crypt survival was significantly greater in the PFD-pre/post and PFD-post groups than in the IR-alone group (p=0.007 and 0.019, respectively).

CONCLUSION

PFD mitigated radiation-induced intestinal injury, and post-IR administration was associated with potentially greater efficacy.