Kick Jochen, Hauser Balázs, Bracht Hendrik, Albicini Maura, Oter Sükrü, Simon Florian, Ehrmann Ulrich, Garrel Catherine, Sträter Jörn, Brückner Uwe B, Leverve Xavier M, Schelzig Hubert, Speit Günter, Radermacher Peter, Muth Claus-Martin
Abteilung Thorax- und Gefässchirurgie, Universitätsklinikum Ulm, Steinhövelstrasse 9, 89075, Ulm, Germany.
Intensive Care Med. 2007 Apr;33(4):694-702. doi: 10.1007/s00134-006-0518-6. Epub 2007 Jan 20.
We previously reported in healthy volunteers that a cantaloupe melon extract chemically combined with wheat gliadin (melon extract/gliadin) and containing SOD, catalase and residual glutathione peroxidase (GPx), protected against DNA strand-break damage induced by hyperbaric oxygen (HBO), a well-established model of DNA damage resulting from oxidative stress. Aortic cross-clamping is a typical example of ischemia/reperfusion injury-related oxidative stress, and therefore we investigated whether this melon extract/gliadin would also reduce DNA damage after aortic cross-clamping and reperfusion.
Prospective, randomized, controlled experimental study.
Animal laboratory.
18 anesthetized, mechanically ventilated and instrumented pigs.
After 14 days of oral administration of 1250 mg of the melon extract/gliadin (n=9) or vehicle (n=9), animals underwent 30 min of thoracic aortic cross-clamping and 4 h of reperfusion.
Before clamping, immediately before declamping, and at 2 and 4 h of reperfusion, we measured blood isoprostane (immunoassay) and malondialdehyde concentrations (fluorimetric thiobarbituric acid test), SOD, catalase and GPx activities (spectrophotometric kits), NO formation (nitrate+nitrite; chemoluminescence), DNA damage in whole blood samples and isolated lymphocytes exposed to hyperbaric oxygen (comet assay). Organ function was also evaluated. Kidney and spinal cord specimen were analysed for apoptosis (TUNEL assay). The melon extract/gliadin blunted the DNA damage, reduced spinal cord apoptosis and attenuated NO release, however, without any effect on lipid peroxidation and organ function.
Pre-treatment with the oral melon extract/gliadin may be a therapeutic option to reduce oxidative cell injury affiliated with aortic cross-clamping.
我们之前在健康志愿者中报告过,一种与小麦醇溶蛋白化学结合的哈密瓜提取物(瓜提取物/醇溶蛋白),含有超氧化物歧化酶(SOD)、过氧化氢酶和残余的谷胱甘肽过氧化物酶(GPx),可保护机体免受高压氧(HBO)诱导的DNA链断裂损伤,HBO是一种由氧化应激导致DNA损伤的成熟模型。主动脉交叉钳夹是缺血/再灌注损伤相关氧化应激的典型例子,因此我们研究了这种瓜提取物/醇溶蛋白是否也能减少主动脉交叉钳夹和再灌注后的DNA损伤。
前瞻性、随机、对照实验研究。
动物实验室。
18头麻醉、机械通气并安装仪器的猪。
在口服1250毫克瓜提取物/醇溶蛋白(n = 9)或赋形剂(n = 9)14天后,动物接受30分钟的胸主动脉交叉钳夹和4小时的再灌注。
在钳夹前、即将松开钳夹前以及再灌注2小时和4小时时,我们测量了血液中异前列腺素(免疫测定法)和丙二醛浓度(荧光硫代巴比妥酸试验)、SOD、过氧化氢酶和GPx活性(分光光度试剂盒)、一氧化氮生成(硝酸盐+亚硝酸盐;化学发光法)、全血样本和暴露于高压氧的分离淋巴细胞中的DNA损伤(彗星试验)。还评估了器官功能。对肾脏和脊髓标本进行凋亡分析(TUNEL试验)。瓜提取物/醇溶蛋白减轻了DNA损伤,减少了脊髓凋亡并减弱了一氧化氮释放,然而,对脂质过氧化和器官功能没有任何影响。
口服瓜提取物/醇溶蛋白预处理可能是减少与主动脉交叉钳夹相关的氧化细胞损伤的一种治疗选择。