Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia
Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia
复制标题
DOI：
10.1097/ccm.0b013e31824e6713
复制
发表时间：
2012-07-01
影响因子：
8.8
通讯作者：
Lasocki, Sigismond
中科院分区：
文献类型：
--
作者：
Heming, Nicholas;Letteron, Philippe;Lasocki, Sigismond
目的：贫血在危重病人中很常见，其原因是炎症和失血。贫血可能与铁缺乏和低血清铁调素水平有关。然而，在这种情况下，铁的管理仍然存在争议，因为它的潜在毒性，包括氧化应激诱导和脓毒症的促进。这项工作的目的是确定铁管理的疗效和毒性，使用模拟重症监护贫血的小鼠模型以及急性败血症的模型。设计：前瞻性，随机，开放标签对照动物研究。设置：大学为基础的研究实验室。受试者：C57 BL/6和OF 1小鼠。干预措施：在C57 BL/6小鼠中腹膜内注射酵母聚糖诱导全身性炎症，随后在我们的完整模型中进行重复放血。在第5天静脉注射相当于15 mg/kg羧基麦芽糖铁的剂量。为了评估铁在败血症模型中的毒性，OF 1小鼠同时注射铁和不同的Escherichia coli strain. Measures和主要结果：为了研究铁对氧化应激的影响，我们测量了活性氧在血液中的生产使用鲁米诺放大化学发光和超氧化物歧化酶2在肝脏中的信使RNA水平。这些氧化应激标志物增加后，铁管理在对照组小鼠，但不是在酵母多糖治疗的小鼠。铁处理的对照小鼠的肝脏过氧化氢酶信使RNA水平降低。在败血症模型或全身炎症模型中，铁给药与死亡率增加无关。铁增加血红蛋白水平的小鼠喂养低铁饮食和静脉切开术和酵母多糖2 wks后治疗administration.Conclusions：在我们的动物模型中，静脉内补充铁的不利影响似乎是最小的。此外，铁似乎是有效的纠正贫血，尽管炎症。铁在危重患者中的有效性和安全性研究是必要的。(Crit Care Med 2012;40：2141-2148）
Objective: Anemia is common in critically ill patients, due to inflammation and blood loss. Anemia can be associated with iron deficiency and low serum hepcidin levels. However, iron administration in this setting remains controversial because of its potential toxicity, including oxidative stress induction and sepsis facilitation. The objective of this work was to determine the efficacy and toxicity of iron administration using a mouse model mimicking critical care anemia as well as a model of acute septicemia.Design: Prospective, randomized, open label controlled animal study.Setting: University-based research laboratory.Subjects: C57BL/6 and OF1 mice.Interventions: Intraperitoneal injection of zymosan inducing generalized inflammation in C57BL/6 mice, followed in our full model by repeated phlebotomies. A dose equivalent to 15 mg/kg of ferric carboxymaltose was injected intravenously on day 5. To assess the toxicity of iron in a septicemia model, OF1 mice were simultaneously injected with iron and different Escherichia coli strains.Measurements and Main Results: To investigate the effect of iron on oxidative stress, we measured reactive oxygen species production in the blood using luminol-amplified chemiluminescence and super-oxide dismutase 2 messenger RNA levels in the liver. These markers of oxidative stress were increased after iron administration in control mice but not in zymosan-treated mice. Liver catalase messenger RNA levels decreased in iron-treated control mice. Iron administration was not associated with increased mortality in the septicemia model or in the generalized inflammation model. Iron increased hemoglobin levels in mice fed with a low iron diet and subjected to phlebotomies and zymosan 2 wks after treatment administration.Conclusions: Adverse effects of intravenous iron supplementation by ferric carboxymaltose seem to be minimal in our animal models. Furthermore, iron appears to be effective in correcting anemia, despite inflammation. Studies of efficacy and safety of iron in critically ill patients are warranted. (Crit Care Med 2012;40:2141-2148)