Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Molecules. 2022 Jun 23;27(13):4036. doi: 10.3390/molecules27134036.
Iron plays a critical role in the immune response to inflammation and infection due to its role in the catalysis of reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions. However, ROS overproduction can be harmful and damage healthy cells. Therefore, iron chelation represents an innovative pharmacological approach to limit excess ROS formation and the related pro-inflammatory mediator cascades. The present study was designed to investigate the impact of the iron chelator, DIBI, in an experimental model of LPS-induced acute lung injury (ALI). DIBI was administered intraperitoneally in the early and later stages of lung inflammation as determined by histopathological evaluation. We found that lung tissues showed significant injury, as well as increased NF-κB p65 activation and significantly elevated levels of various inflammatory mediators (LIX, CXCL2, CCL5, CXCL10, IL-1𝛽, IL-6) 4 h post ALI induction by LPS. Mice treated with DIBI (80 mg/kg) in the early stages (0 to 2 h) after LPS administration demonstrated a significant reduction of the histopathological damage score, reduced levels of NF-κB p65 activation, and reduced levels of inflammatory mediators. Intravital microscopy of the pulmonary microcirculation also showed a reduced number of adhering leukocytes and improved capillary perfusion with DIBI administration. Our findings support the conclusion that the iron chelator, DIBI, has beneficial anti-inflammatory effects in experimental ALI.
铁在炎症和感染的免疫反应中起着关键作用，这是由于它在通过 Haber-Weiss 和 Fenton 反应催化活性氧物种 (ROS) 中的作用。然而，ROS 的过度产生可能是有害的，并会损害健康细胞。因此，铁螯合代表了一种创新的药理学方法，可以限制过多的 ROS 形成和相关的促炎介质级联。本研究旨在研究铁螯合剂 DIBI 在 LPS 诱导的急性肺损伤 (ALI) 实验模型中的影响。根据组织病理学评估，DIBI 通过腹腔内给药在肺炎症的早期和晚期阶段进行给药。我们发现，肺组织显示出明显的损伤，以及 NF-κB p65 激活的增加和各种炎症介质（LIX、CXCL2、CCL5、CXCL10、IL-1β、IL-6）水平的显著升高，在 LPS 诱导的 ALI 后 4 小时。在 LPS 给药后 0 至 2 小时内用 DIBI（80mg/kg）治疗的小鼠显示出组织病理学损伤评分的显著降低，NF-κB p65 激活水平降低，以及炎症介质水平降低。肺微循环的活体显微镜检查还显示，用 DIBI 给药后黏附的白细胞数量减少，毛细血管灌注得到改善。我们的研究结果支持以下结论：铁螯合剂 DIBI 在实验性 ALI 中具有有益的抗炎作用。
