Anti-inflammatory and Antifibrotic Potential of Longidaza in the Bleomycin-induced Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.