Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 IJS Publishing Group Ltd
Συγγραφείς:
Perlikos, F.
Lagiou, M.
Papalois, A.
Rizou, T.
Kroupis, C.
Toumpoulis, I.K.
Περιοδικό:
International Journal of Surgery
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
21 [4 [2,6 bis(1 pyrrolidinyl) 4 pyrimidinyl] 1 piperazinyl]pregna 1,4,9(11) triene 3,20 dione; endothelial nitric oxide synthase; inducible nitric oxide synthase; lazaroid; leukotriene; leukotriene B4 receptor; leukotriene C4; leukotriene C4 synthase; messenger RNA; neuronal nitric oxide synthase; nitric oxide; placebo; reactive oxygen metabolite; antioxidant; endothelial nitric oxide synthase; inducible nitric oxide synthase; neuronal nitric oxide synthase; pregnane derivative; reactive oxygen metabolite, agar gel electrophoresis; animal experiment; animal model; animal tissue; antioxidant activity; aortic occlusion; Article; controlled study; experimental pig; female; fluoroscopy; lipid peroxidation; lung injury; male; mRNA expression level; nonhuman; oxidative stress; priority journal; quantitative analysis; real time polymerase chain reaction; reperfusion injury; reverse transcription polymerase chain reaction; sham procedure; thoracoabdominal aortic occlusion; animal; complication; disease model; drug effect; lipid peroxidation; lung injury; metabolism; peripheral occlusive artery disease; pig; reperfusion injury; synthesis; thoracic aorta, Animals; Antioxidants; Aorta, Thoracic; Arterial Occlusive Diseases; Disease Models, Animal; Lipid Peroxidation; Lung Injury; Male; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pregnatrienes; Reactive Oxygen Species; Reperfusion Injury; Swine
DOI:
10.1016/j.ijsu.2018.05.735
