Antioxidants combined with NO donor enhance systemic inflammation in acute lung injury in rats.
OBJECTIVE
Acute lung injury and acute respiratory distress syndrome (ALI, ARDS) are well-known complications of cardiac and major vascular surgery. ARDS is associated with high mortality and no effective treatment is available. Protective effects of antioxidants or nitric oxide (NO) in experimental studies were not confirmed in clinical trials, but the potential beneficial effects of their combination are poorly known. This study was designed to investigate whether concomitant administration of NO donor and antioxidants has synergic effects on lung protection in ALI.


METHODS
ALI was induced in rats by intestinal ischemia-reperfusion. Superoxide dismutase and catalase were administered as antioxidants and arginine as NO donor. Lung wet-dry ratio, MPO activity, tissue-air ratio, airspace hemorrhage and serum TNF-alpha were used as parameters of lung injury and systemic inflammation.


RESULTS
Antioxidants and arginine significantly reduced lung damage when administered separately. However, concomitant administration of antioxidants and arginine abolished the protective effects and enhanced systemic inflammation.


CONCLUSIONS
Our data suggests that antioxidants and NO in combination should be avoided in clinical practice.
Kiss
Jan
J
Department of Surgery, Turku University Hospital, Turku, Finland. jan.kiss@utu.fi
Kääpä
Pekka
P
Savunen
Timo
T
D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D007249:Inflammation / Q000097:blood / Q000139:chemically induced*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000975:Antioxidants; D020030:Nitric Oxide Donors; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase