Effect of OTR4120 on pulmonary fibrosis in mice

Background Pulmonary fibrosis is a condition characterized by dysregulated tissue repair and remodeling leading to lung tissue scarring. Here, we tested the antifibrotic effect of OTR4120 in a bleomycin-induced mouse model of pulmonary fibrosis. Methods Swiss mice were randomly divided into four experimental groups: a saline-treated control group, an OTR4120 group, a bleomycin-induced fibrosis group with OTR4120 and a bleomycin-induced fibrosis group without OTR4120. Lungs were compared using the lung/body weight index, and the extent of interstitial injury area was graded using histopathological assessment of haematoxylin & eosin-stained lung tissue sections. Lung tissue Collagen I and Collagen III levels, and blood cytokine levels were measured using a Collagen colorimetric kit and a Cytokine colorimetric kit, respectively. Results The group treated by OTR4120, alone were used as a control. The clinical signs in all animals resolved gradually on day 17 after Bleomycin injections and 6 days after OTR4120 treatment, and disappeared almost completely at day 24 after Bleomycin injections and day 13 after OTR4120 treatment. Lung/body weight index values were significantly lower in the bleomycin-OTR4120 treated group versus the bleomycin only group (respectively 7.31; 9.97 and 7.63 mg/g, p<0.01). Histopathological analyses suggest that OTR4120 treatment ameliorated the increased inflammatory cell infiltration, and attenuated the interstitial thickening associated with bleomycin-induced fibrosis. Collagen III and cytokine levels were decreased in the OTR4120 group versus the fibrotic (bleomycin only) group. OTR4120-treated animals were less affected in their behavior, did not lose weight nor appetite, and recovered overall activities within 6 days of OTR4120 treatment, while none of the vehicle-treated animals recovered. Conclusion OTR4120 is a potential candidate to reduce lung fibrosis ### Competing Interest Statement DB is shareholder in OTR3 and RGTA patent inventor