Background: Inflammation, apoptosis and oxidative stress contribute to the development of severe acute pancreatitis-associated acute lung injury (SAP-ALI). Currently, there is no curative treatment for SAP-ALI in the clinic. This study investigated the potential therapeutic role and mechanisms of colchicine in a rat model of SAP-ALI.
Methods: Male Sprague-Dawley rats were randomized and administrated intragastrically with vehicle saline or colchicine (0.5 mg/kg/day) for seven days, followed by injecting sodium taurocholate to induce SAP-ALI. Together with a healthy control group of rats, their pancreatic and lung tissues and plasma samples were collected for histology, enzyme-linked immunosorbent assay (ELISA), immunoblot, immunohistochemistry, and immunofluorescence.
Results: Compared with the sham controls, the SAP group of rats with vehicle saline treatment displayed severe damages, inflammation with many neutrophil and macrophage infiltrates in pancreatic and lung tissues, accompanied by elevated levels of plasma interleukin-1β (IL-1β), IL-6 and tumor necrosis factor (TNF)-α, which were significantly mitigated in colchicine-treated SAP + COL group of rats. Furthermore, colchicine treatment significantly attenuated nuclear factor kappa-B (NF-κB)-p65, signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) phosphorylation, reduced inducible nitric oxide synthase (iNOS) and 4-Hydroxynonenal expression, ROS production and cell apoptosis by decreasing caspase-3 cleavage, Bax expression, but increasing Bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in pancreatic and lung tissues, relative to the SAP group of rats.
Conclusion: Colchicine treatment significantly mitigated the severity of SAP-ALI by inhibiting inflammation, oxidative stress and cell apoptosis in rats.
Keywords: Apoptosis; Colchicine; Inflammation; Oxidative stress; SAP-ALI.
Copyright © 2022. Published by Elsevier Masson SAS.