Effect of Superoxide Dismutase on Bleomycin-Induced Dermal Sclerosis: Implications for the Treatment of Systemic Sclerosis Toshiyuki Yamamoto, Shinsuke.

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Effect of Superoxide Dismutase on Bleomycin-Induced Dermal Sclerosis: Implications for the Treatment of Systemic Sclerosis Toshiyuki Yamamoto, Shinsuke Takagawa, Kiyoshi Nishioka Journal of Investigative Dermatology Volume 113, Issue 5, Pages 843-847 (November 1999) DOI: 10.1046/j.1523-1747.1999.00758.x Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Representative photomicrographs of hematoxylin and eosin (H&E) staining showing effects of SOD on bleomycin-induced dermal sclerosis. Simultaneous treatment of bleomycin and intravenous administration of PC-SOD (3000 U per kg) for 2 wk demonstrated a significant decrease of sclerotic lesions, with slight fibrosis and mild cellular infiltration of mononuclear cells (A). In contrast, mice treated with bleomycin and intravenous administration of 5% mannitol showed a definite sclerotic skin with thickened collagen bundles and homogeneous deposition (B). (Original magnification, ×170.) Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Summary of the effects of SOD on cutaneous histopathology. Shown are the mean±SD of the scores determined as described in Materials and methods. *Groups that were significantly different (p<0.05) from the control mice treated with bleomycin only for each histopathologic parameter. Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Effects of SOD on bleomycin-induced dermal sclerosis. Cutaneous sclerosis was assessed by measurement of skin hydroxyproline content after 3 wk of treatment. Bleomycin-induced cutaneous sclerosis was significantly inhibited by treatment with simultaneous administration of intravenous PC-SOD for 3 wk, compared with that in mice treated with intravenous mannitol (*p<0.05). Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Effects of administration of SOD after onset of dermal sclerosis on the cutaneous histopathology. Intravenous administration of PC-SOD (3000 U per kg) for 2 wk reduced the dermal sclerosis (A), compared with intravenous mannitol treatment (B). (Original magnification, ×170.) Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Effects of post-onset treatment with SOD on cutaneous histopathology. Shown are the mean±SD of the assessment values for the indicated parameters. *Groups that were significantly different (p<0.05) from the control mice treated with bleomycin only for each histopathologic parameter. Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Effects of post-onset administration of SOD on skin hydroxyproline content. Intravenous administration of PC-SOD showed a mild reduction of hydroxyproline content; however, the difference did not reach any significance even when the dose of PC-SOD was increased for up to 30,000 U per kg. Journal of Investigative Dermatology 1999 113, 843-847DOI: (10.1046/j.1523-1747.1999.00758.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions