Protective Effects of a Heme Oxygenase-1-Secreting Lactococcus lactis on Mucosal Injury Induced by Hemorrhagic Shock in Rats

Aim. To investigate the protective effects of a heme oxygenase-1 (HO-1)-secreting Lactococcus lactis (LL-HO-1) on mucosal injury induced by hemorrhagic shock in rats. Methods. The ability of recombinant LL-HO-1 to secrete biological active HO-1 in the rat intestine was determined in sita after 3 d of daily intragastric administration. The therapeutic potential of LL-HO-1 strain was then evaluated on mucosal injury induced by hemorrhagic shock in rats. After successful resuscitation, mean arterial blood pressure was recorded at 5, 10, 20, and 30 min. One hour after resuscitation, the ileum was harvested for evaluation of mucosal injury by blinded microscopic inflammatory score (Chiu's grade 0-5), myeloperoxidase activity, bacterial translocation, and by the secretion of pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-10, respectively). Results. Intragastric administration of HO-1-secreting L lactis strain led to bioactive delivery of HO-1 at intestinal mucosa and significantly enhanced mean arterial blood pressure and interleukin-10 levels. Moreover, intragastric administration of LL-HO-1 significantly decreased Chiu's score, myeloperoxidase activity, bacterial translocation, and tumor necrosis factor-alpha levels when compared with rats treated with the wildtype strain. The protective effect of recombinant LL-HO-1 could be abolished by co-administration of a HO-1 inhibitor, the zinc protoporphyrin-IX. Conclusion. These results suggest that intragastric administration with HO-1-secreting L. lactis reduces mucosal injury induced by hemorrhagic shock. (C) 2009 Elsevier Inc. All rights reserved.