Porous SiO2 -coated ultrasmall selenium particles nanospheres attenuate cerulein-induce acute pancreatitis in mice by downregulating oxidative stress

Objective: To investigate the potential therapeutic role of porous SiO₂ -coated ultrasmall selenium particles nanospheres (Se@SiO₂ nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism.

Methods: C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiO₂ nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg Se@SiO₂ ) groups, respectively. Serum levels of amylase and Lipase, inflammatory cytokines (interleukin [IL]-6, IL-1β and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of Reactive Oxygen Species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue.

Results: Se@SiO₂ nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic Enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, Se@SiO₂ nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1.

Conclusion: Se@SiO₂ nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/MyD88/p-p65 and NQO1/Nrf2/HO-1 pathways.