Protective effects of carbon monoxide releasing molecule‑2 on pancreatic function in septic mice.

Abstract

The present study aimed to investigate the effect of carbon monoxide (CO)-releasing molecule-2 (CORM-2) on pancreatic function in sepsis-model mice. To perform the present investigation, mice were rendered septic by cecal ligation and puncture (CLP). Then, mice were either treated with or without CORM-2 (8 mg/kg, intravenous) for different durations (6, 12 and 24 h) immediately following CLP. The levels of serum amylase and lipase, tumor necrosis factor α, interleukin-1β and interleukin-6 in addition to myeloperoxidase (MPO) activity in pancreatic tissues were determined at 6, 12 and 24 h post-CLP. Histological scores and the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), nuclear factor-κB (NF-κB) and phosphorylated inhibitor of κB (p-IκB-α) in the pancreas were also evaluated at 24 h post-CLP. The results of the present study revealed that compared with CLP-alone group, CORM-2 treatment significantly (P<0.05) reduced the levels of serum amylase, lipase and pro-inflammatory cytokines. In parallel, the severity of pancreatic histology, MPO activity and the expression levels of ICAM-1 and VCAM-1 in the pancreas of CORM-2 treated CLP mice were substantially decreased compared with the untreated group. Furthermore, CORM-2 treatment inhibited the expression levels of NF-κB and P-IκB-α in the pancreas of mice following CLP compared with the untreated group. CORM-2-liberated CO exerted protective effects on the pancreatic function of septic mice, and the beneficial effects may be due to the suppression of NF-κB activation and subsequent regulation of NF-κB-dependent expression of cytokines.