Ypsilantis Petros, Tentes Ioannis, Lambropoulou Maria, Anagnostopoulos Konstantinos, Papadopoulos Nikolaos, Kortsaris Alexandros, Simopoulos Constantinos
Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
J Gastroenterol Hepatol. 2008 Feb;23(2):328-35. doi: 10.1111/j.1440-1746.2007.05154.x. Epub 2007 Sep 12.
Mesna (2-mercaptoethane-sulfonate) has been shown to attenuate oxidative injury induced by ischemia reperfusion (I/R) in the kidneys, the liver, and the intestine; however, its mechanism of action has not been fully elucidated. We sought to determine a prophylactic administration schedule of mesna that would confer optimal antioxidant protection on the intestinal mucosa following I/R and to investigate whether mesna's action is mediated via inhibition of nuclear factor-kappaB (NF-kappaB) activity.
Wistar rats were subjected to one of the following: (a) induction of 30 min ischemia followed by 60 min reperfusion (I30/R60) of the intestine, (b) pretreatment with intraperitoneal or oral mesna at various time- and dose- administration schedules plus I30/R60, (c) sham operation, (d) no operation (controls), or (e) oral mesna alone. At the end of the reperfusion period or at various time points after mesna alone administration, the oxidative state of the intestinal mucosa was assessed in terms of glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity. In addition, NF-kappaB activity in the intestinal mucosa was assessed immunohistochemically in the oral mesna plus I/R and in the oral mesna alone groups.
Sham operation caused mild stress, while I/R caused substantial oxidative stress in the intestinal mucosa. Mesna pretreatment had an antioxidant effect which varied from attenuation to prevention of oxidative stress. Over the two routes of administration, the oral proved to be more effective and had a time- and dose- dependent effect. The antioxidant action of mesna was not related to enhancement of the intestinal mucosa oxidative state. Furthermore, I/R induced NF-kappaB activation in the intestinal mucosa which was inhibited by mesna pretreatment. In the absence of oxidative damage, mesna led to downregulation of activated NF-kappaB.
Prophylaxis with mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-kappaB activation.
美司钠（2-巯基乙烷磺酸盐）已被证明可减轻肾脏、肝脏和肠道缺血再灌注（I/R）诱导的氧化损伤；然而，其作用机制尚未完全阐明。我们试图确定美司钠的预防性给药方案，该方案能在I/R后为肠黏膜提供最佳的抗氧化保护，并研究美司钠的作用是否通过抑制核因子-κB（NF-κB）活性介导。
将Wistar大鼠分为以下几组：（a）诱导肠缺血30分钟，随后再灌注60分钟（I30/R60）；（b）在不同时间和剂量给药方案下，腹腔内或口服美司钠预处理加I30/R60；（c）假手术；（d）未手术（对照组）；或（e）单独口服美司钠。在再灌注期结束时或单独给予美司钠后的不同时间点，根据谷胱甘肽与谷胱甘肽二硫化物的比率、丙二醛浓度和超氧化物歧化酶活性评估肠黏膜的氧化状态。此外，在口服美司钠加I/R组和单独口服美司钠组中，通过免疫组织化学法评估肠黏膜中的NF-κB活性。
假手术引起轻度应激，而I/R在肠黏膜中引起大量氧化应激。美司钠预处理具有抗氧化作用，其作用从减轻氧化应激到预防氧化应激不等。在两种给药途径中，口服给药被证明更有效，且具有时间和剂量依赖性。美司钠的抗氧化作用与增强肠黏膜氧化状态无关。此外，I/R诱导肠黏膜中NF-κB活化，而美司钠预处理可抑制这种活化。在没有氧化损伤的情况下，美司钠导致活化的NF-κB下调。
美司钠预防性给药通过抑制NF-κB活化预防I/R诱导的肠氧化应激。
