Inhibitory effects of a lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis in mice

Oxidant/antioxidant imbalance is thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, antioxidants, such as s uperoxide dismutase (SOD), are expected to have an inhibitory potential aga inst IPF. To elucidate whether a lecithinized SOD (phosphatidylcholine [PC] -SOD) has the potential to be a new therapeutic agent for IPF, we investiga ted the inhibitory effects of PC-SOD at doses of 1 mg/kg/d (low dose) and 1 0 mg/kg/d (high dose)and of methylprednisolone (mPSL) on bleomycin (BLM)-in duced pulmonary fibrosis in mice. Histopathologic evaluation and lung hydro xyproline content revealed that the severity of fibrosis was attenuated in mice treated with low-dose PC-SOD, whereas no significant effect was observ ed in other mice. In bronchoalveolar ravage fluid on Day 1 after treatment with BLM, BLM-induced increases in total cell number, populations of lympho cytes and neutrophils, and expression of messenger RNA for interleukin-1 be ta and platelet-derived growth factor (PDCF)-A were significantly suppresse d in PC-SOD-treated mice. The suppression of PDCF-A expression was signific antly greater in mice treated with low-dose PC-SOD than in mice treated wit h high-dose PC-SOD or mPSL. In summary, this study demonstrated the inhibit ory effects of low-dose PC-SOD on the development of pulmonary fibrosis, wh ich indicates the potential usefulness of PC-SOD as a new treatment agent f or IPF or at least for BLM-induced pulmonary fibrosis in humans.