Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats

Introduction: This experimental setting was undertaken to elucidate and confirm the role of inflammatory and oxidant-antioxidant mechanisms on blunt injury induced moderate pulmonary contusion (PC). We intended to determine the effects of dexamethasone (DXM), N-acetylcysteine (NAC) and aprotinin (APR) in terms of their ability to diminish the consequences of acute lung injury due to PC. Methods: Rats were allocated to five subgroups. Except for the control, all subgroups had a moderate pulmonary contusion. Following 45 min of observation, animals in groups I and II received intraperitoneal saline, group III 10 mg/kg DXM, group IV 500 mg/kg NAC and group V 30,000 kIU/ml APR. After the procedure, 6 h after contusion, blood gas analysis, lung tissue nitric oxide (NO) and malondialdehyde (MDA) levels, Superoxide dismutase (SOD) and catalase (CAT) activity, bronchoalveolar lavage (BAL) fluid and histopathological examination were performed. Results: All PaO2 values decreased significantly in contused rats as compared with the control group (p < 0.05). DXM, NAC and APR resulted in a slight increase in PaO2 values compared with group II (p < 0.05). Lung tissue levels of MDA and NO were higher in the contusion group than in the control (p < 0.05). DXM, NAC and APR all decreased the levels of MDA and NO (p < 0.05), however the decrease in NO was not found to be significant with APR (p > 0.05). SOD and CAT activities increased significantly after contusion compared to control group (p < 0.05). There was no significant difference even though SOD levels were elevated in groups III, IV and V compared with contused animals (p > 0.05). Neutrophils in BAL fluid significantly increased in contused animals (p < 0.05). Only DXM significantly decreased neutrophil population in BAL fluid (p < 0.05). Scores for alveolar haemorrhage/oedema were higher in all contusion-performed rats than those in the control (p < 0.05). Compared with the other drugs, only APR significantly improved the haemorrhage/oedema scores compared to sham animals (p = 0.024). Conclusions: Our findings demonstrate that moderate bilateral PC induced by blunt chest trauma leads to an early inflammatory process which is clearly associated with activation of the oxidant-antioxidant cascade. On this basis, early supportive treatment with DXM, NAC and APR may yield favourable results on pulmonary pathophysiological parameters which are adversely affected due to PC. (C) 2008 Elsevier Ltd. All rights reserved.