Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1279-1284

Inhibitory Effects of a Lecithinized Superoxide Dismutase on Bleomycin-Induced Pulmonary Fibrosis in Mice

KOTARO TAMAGAWA, YASUYUKI TAOOKA, AKIHIRO MAEDA, KEIKO HIYAMA, SHINICHI ISHIOKA, and MICHIO YAMAKIDO

Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan

Oxidant/antioxidant imbalance is thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, antioxidants, such as superoxide dismutase (SOD), are expected to have an inhibitory potential against IPF. To elucidate whether a lecithinized SOD (phosphatidylcholine [PC]-SOD) has the potential to be a new therapeutic agent for IPF, we investigated the inhibitory effects of PC-SOD at doses of 1 mg/kg/d (low dose) and 10 mg/kg/d (high dose) and of methylprednisolone (mPSL) on bleomycin (BLM)-induced pulmonary fibrosis in mice. Histopathologic evaluation and lung hydroxyproline content revealed that the severity of fibrosis was attenuated in mice treated with low-dose PC-SOD, whereas no significant effect was observed in other mice. In bronchoalveolar lavage fluid on Day 1 after treatment with BLM, BLM-induced increases in total cell number, populations of lymphocytes and neutrophils, and expression of messenger RNA for interleukin-1 and platelet-derived growth factor (PDGF)-A were significantly suppressed in PC-SOD-treated mice. The suppression of PDGF-A expression was significantly greater in mice treated with low-dose PC-SOD than in mice treated with high-dose PC-SOD or mPSL. In summary, this study demonstrated the inhibitory effects of low-dose PC-SOD on the development of pulmonary fibrosis, which indicates the potential usefulness of PC-SOD as a new treatment agent for IPF or at least for BLM-induced pulmonary fibrosis in humans.

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