Phospholipase A2 (PLA2) has been known to be involved in the pathogenesis of acute lung injury (ALI) including ARDS. Since doxycycline has the property of inhibiting secretory group II PLA2, the therapeutic effect of doxycycline hyclate was investigated for gut ischemia/reperfusion (I/R)-induced ALI in Sprague-Dawley rats.

ALI was induced in Sprague-Dawley rats by clamping of the superior mesenteric artery for 60 min, followed by 120 min of reperfusion. To confirm the pathogenetic mechanisms of this ALI associated with neutrophilic oxidative stress, we measured bronchoalveolar lavage (BAL) protein content and lung MPO, and performed cyto chemical electron microscopy for detection of free radicals, assay of PLA2 activity and cytochrome-c reduction assay.

In gut I/R-induced ALI rats, protein leakage, pulmonary neutrophil accumulation, free radical production and lung PLA2 activity were all increased. These effects were reversed by doxycycline hyclate.

Doxycycline appars to be effective in ameliorating the gut I/R-induced ALI by inhibiting PLA2, thereby decreasing the production of free radicals from neutrophils.