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.

This article has been cited by other articles:

				T. Ishihara, K.-I. Tanaka, Y. Tasaka, T. Namba, J. Suzuki, T. Ishihara, S. Okamoto, T. Hibi, M. Takenaga, R. Igarashi, et al. Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 152 - 164. [Abstract] [Full Text] [PDF]

				S. Tajima, M. Bando, Y. Ishii, T. Hosono, H. Yamasawa, S. Ohno, T. Takada, E. Suzuki, F. Gejyo, and Y. Sugiyama Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice Eur. Respir. J., November 1, 2008; 32(5): 1337 - 1343. [Abstract] [Full Text] [PDF]

				A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]

				A. Nakatani-Okuda, H. Ueda, S.-i. Kashiwamura, A. Sekiyama, A. Kubota, Y. Fujita, S. Adachi, Y. Tsuji, T. Tanizawa, and H. Okamura Protection against bleomycin-induced lung injury by IL-18 in mice Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L280 - L287. [Abstract] [Full Text] [PDF]

				M. Mata, A. Ruiz, M. Cerda, M. Martinez-Losa, J. Cortijo, F. Santangelo, A. Serrano-Mollar, A. Llombart-Bosch, and E.J. Morcillo Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats Eur. Respir. J., December 1, 2003; 22(6): 900 - 905. [Abstract] [Full Text] [PDF]

				T. Hoshino, H. Nakamura, M. Okamoto, S. Kato, S. Araya, K. Nomiyama, K. Oizumi, H. A. Young, H. Aizawa, and J. Yodoi Redox-active Protein Thioredoxin Prevents Proinflammatory Cytokine- or Bleomycin-induced Lung Injury Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1075 - 1083. [Abstract] [Full Text] [PDF]

				H. Ishii, H. Mukae, T. Kakugawa, T. Iwashita, H. Kaida, T. Fujii, T. Hayashi, J.-i. Kadota, and S. Kohno Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L957 - L963. [Abstract] [Full Text] [PDF]

				V. L. Kinnula and J. D. Crapo Superoxide Dismutases in the Lung and Human Lung Diseases Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1600 - 1619. [Abstract] [Full Text] [PDF]

				A. Pardo, V. Ruiz, J. L. Arreola, R. Ramirez, J. Cisneros-Lira, M. Gaxiola, R. Barrios, S. V. Kala, M. W. Lieberman, and M. Selman Bleomycin-induced Pulmonary Fibrosis Is Attenuated in {gamma}-Glutamyl Transpeptidase-Deficient Mice Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 925 - 932. [Abstract] [Full Text] [PDF]

				M. Koval Sharing signals: connecting lung epithelial cells with gap junction channels Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L875 - L893. [Abstract] [Full Text] [PDF]

				H. Matsuoka, T. Arai, M. Mori, S. Goya, H. Kida, H. Morishita, H. Fujiwara, I. Tachibana, T. Osaki, and S. Hayashi A p38 MAPK inhibitor, FR-167653, ameliorates murine bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L103 - L112. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Tuberculosis, Lung Infections, and Interstitial Lung Disease in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1774 - 1788. [Full Text] [PDF]

				R. P. Bowler, M. Nicks, K. Warnick, and J. D. Crapo Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L719 - L726. [Abstract] [Full Text] [PDF]