Intravenous superoxide dismutase administration reduces contralateral lung injury induced by unilateral lung ischemia and reperfusion in rats through suppression of activity and protein expression of matrix metalloproteases.

ABSTRACT

BACKGROUND: Ischemia and reperfusion (I/R) of the lungs induces massive superoxide radical production. On the other hand, matrix metalloproteases (MMPs) were shown to play an essential role in I/R-associated lung injury. We aimed to investigate the lung-protective efficacy of intravenous superoxide dismutase (SOD) administration and its relation with MMPs activity in the lungs subsequent to I/R injury. METHODS: Twenty-two male Sprague-Dawley rats were divided into a sham group (n = 6), a unilateral lung I/R group (n = 8), and a SOD-treated lung I/R group (n = 8). Unilateral lung ischemia was conducted by occluding the left lung hilum for 90 min, followed by 5 hours of reperfusion through release of the occlusion. In the SOD-treated group, SOD was administered intravenously during the first hour of reperfusion. We assessed the protein contents in the broncho-alveolar lavage fluid (PCBAL) as a marker for protein permeability and lung wet-to-dry weight ratio (W/D) for lung water content. We also measured levels of lipid peroxidation and MMP activity in the lungs, by tissue malonedealdehyde (MDA) level with the use of enzyme-linked immunoassay, and the gelatin zymography technique, respectively. RESULTS: Forty-eight hours of left-lung I/R significantly increased PCBAL (P < .001), W/D (P < .05), tissue MDA level (P < .05), and MMP-9 and MMP-2 activity. SOD treatment attenuated I/R-induced contralateral lung injury, reducing pulmonary permeability, lipid peroxidation, and MMP activities. CONCLUSIONS: I/R injury of the left lung induced increases in W/D, PCBAL, MDA level, and MMP-9 activity in the right lung. SOD treatment during the first hour of a 5-hour reperfusion protected the lung through suppressing MMP-9 activity and reducing tissue lipid peroxidation.