Lazaroid (U-74389G) ameliorates lung injury due to lipid peroxidation and nitric oxide synthase-dependent reactive oxygen species generation caused by remote systematic ischemia-reperfusion following thoracoabdominal aortic occlusion. (July 2018)

• Record Type: Journal Article
• Authors: Perlikos, Fotis; Lagiou, Maria; Papalois, Apostolos; Rizou, Tatiana; Kroupis, Christos; Toumpoulis, Ioannis K.
• Is Part Of: International journal of surgery. Volume 55(2018)
• Page Start: 156
• Page End: 161
• Publication Date: 2018-07
• Subjects: Lazaroid -- Aortic occlusion -- Lung ischemia-reperfusion injury -- Real-time RT-qPCR; Surgery -- Periodicals; Surgical Procedures, Operative -- Periodicals; 617.005
• DOI: 10.1016/j.ijsu.2018.05.735
• Languages: English
• ISSNs: 1743-9191

Abstract

Abstract: Introduction: Lung ischemia-reperfusion injury after thoracoabdominal aortic occlusion represents a major complication, which increases morbidity and mortality. In the present study we hypothesized that lazaroid U-74389G intravenous administration protects from lung ischemia-reperfusion injury through lipid peroxidation inhibition. Materials and methods: A total of 24 pigs were randomized in three groups. Group I (n = 8) underwent sham operation, group II (n = 8) underwent thoracoabdominal aortic occlusion for 45min and received placebo and group III (n = 8) received 3 doses of lazaroid (3 mg/kg) 60 and 30min before thoracoabdominal aortic occlusion and at 30min during thoracoabdominal aortic occlusion (duration 45min). Aortic occlusion was performed with aortic balloon-catheters under fluoroscopic guidance. All animals were sacrificed at the 7 t h postoperative day and lung specimens were harvested for molecular analysis. Results: mRNA levels of leukotrienes LB4 (LTB4R2), LC4 (LTC4S) and nitric oxide synthase (NOS) isoforms including iNOS, nNOS and eNOS were determined with real-time RT-qPCR. Nitric oxide can either induce (iNOS) or inhibit (nNOS and eNOS) lipid peroxidation based on its specific isoform origin. Group III showed significantly reduced mRNA levels of LTB4R2 (−63.7%), LTC4S (−35.9%) and iNOS (−60.2%) when compared with group II (P < 0.05, for all). The mRNA levels of nNOS was significantly increased (+37.4%), while eNOS was slightly increased (+2.1%) in group III when compared with group II (P < 0.05 and P = 0.467 respectively). Conclusion: Lazaroid U-74389G may represent an effective pharmacologic intervention in reducing lung ischemia-reperfusion injury following thoracoabdominal aortic occlusion. Highlights: Lipid peroxidation plays a significant role in lung injury by remote systematic ischemia-reperfusion after aortic aneurysm replacement. Our results demonstrate significant decrease in lung lipid peroxidation 7 days after. It is the first study to address this beneficial effect. The detection of leukotrienes and NOS isoforms may represent novel biomarkers for the early and midterm lung ischemia/reperfusion injury.