Fernández Virginia, Vargas Romina, Castillo Valentina, Cádiz Nicolás, Bastías Daniela, Román Sebastián, Tapia Gladys, Videla Luis A
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70000, Santiago 7, Chile.
ScientificWorldJournal. 2013 Oct 27;2013:607285. doi: 10.1155/2013/607285. eCollection 2013.
The role of iron (Fe)-induced prooxidant status in Fe preconditioning against ischemia (1 h)-reperfusion (20 h) induced liver injury was assessed using N-acetylcysteine (NAC) (1 g/kg) before Fe (50 mg/kg), given to male Sprague Dawley rats on alternate days during 10 days. IR significantly increased serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, with drastic changes in liver histology, hepatic glutathione depletion, and nuclear factor-κB (NF-κB) p65 diminution (P < 0.05) (ELISA). Fe-induced liver oxidative stress, as evidenced by higher protein carbonyl/glutathione content ratios (P < 0.05) at days 11 and 12 after treatment, was abolished by NAC. Under these conditions, short-term Fe administration exerted significant protection against IR liver injury, as shown by 85% and 60% decreases in IR-induced serum AST and ALT (P < 0.05), respectively, and normalization of hepatic histology, glutathione levels, and NF-κB activation, changes that were suppressed by NAC administration prior to Fe. Results of this study indicate that NAC administration prior to an iron protocol reestablishes IR liver injury, supporting the role of Fe-induced transient oxidative stress in hepatoprotection and its potential clinical application.
在10天内，每隔一天给雄性Sprague Dawley大鼠腹腔注射铁（50mg/kg），在注射铁之前1小时腹腔注射N-乙酰半胱氨酸（NAC，1g/kg），以此评估铁（Fe）诱导的促氧化状态在铁预处理对抗缺血（1小时）-再灌注（20小时）诱导的肝损伤中的作用。缺血-再灌注（IR）显著升高血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平，同时肝脏组织学发生剧烈变化、肝谷胱甘肽耗竭以及核因子-κB（NF-κB）p65减少（P<0.05）（酶联免疫吸附测定）。NAC消除了铁诱导的肝脏氧化应激，这在治疗后第11天和第12天表现为较高的蛋白质羰基/谷胱甘肽含量比（P<0.05）。在这些条件下，短期给予铁对IR肝损伤具有显著保护作用，表现为IR诱导的血清AST和ALT分别降低85%和60%（P<0.05），肝脏组织学、谷胱甘肽水平和NF-κB激活恢复正常，而在给予铁之前给予NAC可抑制这些变化。本研究结果表明，在铁给药方案之前给予NAC可重新引发IR肝损伤，支持铁诱导的短暂氧化应激在肝脏保护中的作用及其潜在的临床应用。
