Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats.
BACKGROUND
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 PaO(2) 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 PaO(2) 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.
Türüt
Hasan
H
Department of Thoracic Surgery, Kahramanmaras Sutcu Imam University Medical School, Kahramanmaras, Turkey. drhasanturut@yahoo.com
Ciralik
Harun
H
Kilinc
Metin
M
Ozbag
Davut
D
Imrek
Secil Simsek
SS
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D016877:Oxidants / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014949:Wounds, Nonpenetrating / Q000378:metabolism*
D016166:Free Radical Scavengers; D016877:Oxidants; D009569:Nitric Oxide; D008315:Malondialdehyde; D003907:Dexamethasone; D007611:Aprotinin; D002374:Catalase; D013482:Superoxide Dismutase; D000111:Acetylcysteine