ceruletide and yttria

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.

Topics: Acute Disease; Animals; Antioxidants; Biomarkers; Ceruletide; Endoplasmic Reticulum Stress; Inflammation; Lipid Peroxidation; Lipopolysaccharides; Macrophages; Male; Membrane Potential, Mitochondrial; Mice; Nanoparticles; Neutrophils; Nitrosation; Oxidation-Reduction; Oxidative Stress; Pancreas; Pancreatitis; RAW 264.7 Cells; Reactive Oxygen Species; Severity of Illness Index; Transcription Factor RelA; Yttrium