Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Department of Biotechnology, Indian Institute of Technology-Roorkee, Roorkee, Uttarakhand, India.
Nanomedicine. 2019 Jun;18:54-65. doi: 10.1016/j.nano.2019.02.018. Epub 2019 Mar 6.
Oxidative stress plays a major role in acute pancreatitis (AP), leading to massive macrophage infiltration. Nanoyttria (NY) possesses potent free radical scavenging activity. As reactive oxygen species and inflammation play major role in AP, we hypothesized that NY may alleviate cerulein induced AP. NY ameliorated LPS induced oxidative stress in vitro. It reduced ROS, superoxide radical generation and restored the mitochondrial membrane potential in macrophages. Interestingly, NY reduced plasma amylase and lipase levels and attenuated the mitochondrial stress and inflammatory markers. NY suppressed the recruitment of inflammatory cells around the damaged pancreatic acinar cells. Furthermore, NY intervention perturbed the course of AP via reduction of endoplasmic reticulum (ER) stress markers (BiP, IRE1 and Ero1-Lα), and molecular chaperones (Hsp27 and Hsp70). We, to the best of our knowledge, report for first time that NY can attenuate experimental AP by restoration of mitochondrial and ER homeostasis through Nrf2/NFκB pathway modulation.
氧化应激在急性胰腺炎 (AP) 中起主要作用，导致大量巨噬细胞浸润。纳米氧化钇 (NY) 具有很强的自由基清除活性。由于活性氧和炎症在 AP 中起主要作用，我们假设 NY 可能减轻鹅膏蕈碱诱导的 AP。NY 在体外减轻了 LPS 诱导的氧化应激。它减少了 ROS、超氧自由基的产生，并恢复了巨噬细胞中的线粒体膜电位。有趣的是，NY 降低了血浆淀粉酶和脂肪酶水平，并减弱了线粒体应激和炎症标志物。NY 抑制了受损胰腺腺泡细胞周围炎症细胞的募集。此外，NY 通过减少内质网 (ER) 应激标志物 (BiP、IRE1 和 Ero1-Lα) 和分子伴侣 (Hsp27 和 Hsp70) 的干预改变了 AP 的进程。据我们所知，这是首次报道 NY 可以通过调节 Nrf2/NFκB 通路来恢复线粒体和 ER 平衡，从而减轻实验性 AP。
