Attenuation effects of heparin–superoxide dismutase conjugate on bleomycin-induced lung fibrosis in vivo and radiation-induced inflammatory cytokine expression in vitro

In this study, the effects of heparin–superoxide dismutase conjugate (heparin–SOD) on bleomycin-induced pulmonary fibrosis in vivo and on inflammatory cytokine expression in vitro were evaluated. To investigate the effects of heparin–SOD on pulmonary fibrosis, heparin–SOD was administered to bleomycin (BLM)-treated mice by intraperitoneal injection once a day and the hydroxyproline content in lung was determined per 7 days. The degree of fibrosis was assessed quantitatively using histopathologic features. The results showed that heparin–SOD inhibited BLM-induced lung fibrotic lesions as reflected by the decrease of lung hydroxyproline content and lung fibrosis grade 28 days after BLM instillation. The in vitro effects on the cytokine level expressed by irradiated 3T3 fibroblasts showed that heparin–SOD significantly lowered the levels of transforming growth factor-β1 and interleukin-1β. These results strongly demonstrated that heparin–SOD might be useful in the prevention and treatment of pulmonary fibrosis.