Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.
Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.
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DOI：
10.2147/ijn.s53032
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发表时间：
2013
影响因子：
8
通讯作者：
Bhargava K
中科院分区：
文献类型：
--
作者：
Arya A;Sethy NK;Singh SK;Das M;Bhargava K
氧化铈纳米颗粒在细胞培养和动物模型中可以有效地猝灭活性氧物种(ROS)。尽管据报道，纳米氧化钙沉积在肺中，但它们在氧化应激期间提供肺保护的有效性仍未被探索。因此，本研究评估了纳米氧化钙对大鼠肺组织在低压缺氧时的保护作用。将48只动物随机分为4组(对照组[C]、纳米氧化钙组[T]、缺氧组[H]和纳米氧化钙+缺氧组[T+H])。分别以0.5μg/kg体重/周注射纳米氧化钙(T组和T+H组)或赋形剂(C组和H组)，连续5周。末次给药后，H组和T+H组动物接受低压低氧刺激，C组和T组动物维持常氧状态。分离肺组织，提取匀浆，用于分析ROS、脂质过氧化、谷胱甘肽、蛋白质羰化和4-羟基壬醛加合物的形成。采用酶联免疫吸附试验检测血浆中主要炎性细胞因子。固定完整的肺组织，分别进行透射电子显微镜和组织病理学检查，以检测纳米颗粒的内化以及肺形态的改变。采用微乳液法制备了直径为7~10 nm的球形纳米氧化钙，并对其在低压低氧条件下的肺保护作用进行了评价。通过多次腹腔注射低摩尔浓度的纳米微囊，我们成功地定位了纳米微囊在啮齿动物肺中的位置，没有任何炎症反应。肺沉积的纳米钙限制了ROS的形成、脂质过氧化和谷胱甘肽的氧化，并阻止了低压缺氧时的氧化蛋白质修饰，如硝化和羰基的形成。我们还观察到注射纳米氧化钙的肺部炎症减轻，支持纳米氧化钙的抗炎特性。总而言之，这些结果表明纳米氧化钙沉积在肺中，在低压缺氧时通过消除有毒自由基来提供保护，并且不会引起任何炎症反应。
Cerium oxide nanoparticles (nanoceria) are effective at quenching reactive oxygen species (ROS) in cell culture and animal models. Although nanoceria reportedly deposit in lungs, their efficacy in conferring lung protection during oxidative stress remains unexplored. Thus, the study evaluated the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia. A total of 48 animals were randomly divided into four equal groups (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5 μg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H groups) for 5 weeks. After the final dose, H and T+H animals were challenged with hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were isolated and homogenate was obtained for analysis of ROS, lipid peroxidation, glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma was used for estimating major inflammatory cytokines using enzyme-linked immunosorbent assay. Intact lung tissues were fixed and both transmission electron microscopy and histopathological examinations were carried out separately for detecting internalization of nanoparticles as well as altered lung morphology. Spherical nanoceria of 7–10 nm diameter were synthesized using a microemulsion method, and the lung protective efficacy of the nanoceria evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria. Cumulatively, these results suggest nanoceria deposit in lungs, confer protection by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any inflammatory response.