Effect of pretreatment with high-dose ulinastatin in preventing radiation-induced pulmonary injury in rats

In order to develop a better management strategy for radiation-induced pulmonary injury, we compared the protective effect of pretreatment and aftertreatment with different doses of ulinastatin. Two hundred and forty female Sprague-Dawley rats were randomized into five groups. Group R received radiation only, groups PI and P2 were pretreated with different doses of i.v. ulinastatin for 3 days pre- and 4 days post-irradiation, and groups A1 and A2 were treated for 7 days post-irradiation only. Rats were sacrificed at 2 h, and at 4, 8,16, and 24 weeks post-irradiation. The expressions of TGF-beta 1, TNF-alpha, IL-6, hydroxyproline and laminin were determined. No adverse toxicological effects of ulinastatin pretreatment were observed. Mortality and ratio of fibrotic area was lowest in group P1(5/45; 30.6 +/- 3.11%, P<0.05 vs. A2). Expressions of TGF-beta 1 and IL-6 in group P1 were significantly lowest at 4 weeks (3.01 +/- 035, 549 +/- 58, 32.3 +/- 3.27, P<0.01), and expressions of hydroxyproline and laminin were also lowest at 24 weeks (741 +/- 68 and 82.6 +/- 6.91, P<0.01) in comparison with other groups. Significant differences were observed in expression of TGF-beta 1 and TNF-alpha in lung between group P1 and group A1 at 4 weeks (263 +/- 11% vs. and 187 +/- 9%, 189 +/- 8% vs. 154 +/- 9%, P<0.01, P<0.05 respectively). Pretreatment with high dose ulinastatin resulted in a milder inflammatory response and suppressed pulmonary fibrosis, which may serve as a favorable management strategy. (C) 2008 Elsevier B.V. All rights reserved.