Cherif-Sayadi Amani, Hadj Ayed-Tka Kaouther, Bejaoui Mohamed, Ben Gdara Neyla, Zaouali Mohamed Amine, Ben Abdennebi Hassen
Research Unit (UR12ES11) Molecular Biology and Anthropology Applied to Development and Health, Department of Physiology, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Ann Transplant. 2016 Sep 27;21:602-610. doi: 10.12659/aot.899338.
BACKGROUND The ability of nitrite to provide protection following ischemia/reperfusion (I/R) has been demonstrated, but its mechanism is still poorly understood. This study aimed to determine the optimal nitrite concentration to add into Institut Georges Lopez (IGL-1) storage solution and to assess its effect on antioxidant enzymes and autophagy. MATERIAL AND METHODS Livers from Sprague-Dawley rats were conserved in IGL-1 for 24 hours at 4°C or in IGL-1 enriched with nitrite at 50, 500 and 1,000 nM, respectively, before being perfused ex-vivo at 37 °C for 120 minutes. Sham livers were perfused ex vivo without cold preservation. RESULTS All biological and functional parameters of the preserved livers were significantly impaired as compared to shams. Interestingly, the supplementation of nitrite to IGL-1 protected the liver from I/R injury. Among the doses of nitrite evaluated, the 50 nM was proved efficient: it significantly reduced cytolysis, mitochondrial damage, and lipid peroxidation, and enhanced antioxidant enzyme activity (superoxide dismutase, catalase, and glutathione peroxidase activity) and hepatic function parameters (portal resistance, bile flow, and bromosulfophthalein clearance). In addition, increased levels of the autophagy parameters were observed when 50 nM of nitrite were added to IGL-1 solution, but this effect disappeared completely with higher concentrations of nitrite. CONCLUSIONS It seems that 50 nM of nitrite added to IGL-1 is the optimal concentration able to maintain cell integrity and hepatic function through autophagy induction and oxidative stress prevention.
背景 亚硝酸盐在缺血/再灌注（I/R）后提供保护的能力已得到证实，但其机制仍知之甚少。本研究旨在确定添加到乔治·洛佩斯研究所（IGL-1）保存液中的最佳亚硝酸盐浓度，并评估其对抗氧化酶和自噬的影响。材料与方法 将来自Sprague-Dawley大鼠的肝脏分别在4°C下于IGL-1中保存24小时，或在分别添加了50、500和1000 nM亚硝酸盐的IGL-1中保存，然后在37°C下进行120分钟的离体灌注。假手术组的肝脏未进行冷保存直接进行离体灌注。结果 与假手术组相比，保存肝脏的所有生物学和功能参数均明显受损。有趣的是，向IGL-1中添加亚硝酸盐可保护肝脏免受I/R损伤。在所评估的亚硝酸盐剂量中，50 nM被证明是有效的：它显著降低了细胞溶解、线粒体损伤和脂质过氧化，并增强了抗氧化酶活性（超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性）以及肝功能参数（门静脉阻力、胆汁流量和溴磺酚酞清除率）。此外，当向IGL-1溶液中添加50 nM亚硝酸盐时，自噬参数水平升高，但在更高浓度的亚硝酸盐作用下，这种效应完全消失。结论 似乎向IGL-1中添加50 nM亚硝酸盐是能够通过诱导自噬和预防氧化应激来维持细胞完整性和肝功能的最佳浓度。
