Fetal liver injury ameliorated by migration inhibitory factor inhibition in a rat model of acute pancreatitis in pregnancy.

Abstract

This study was designed to investigate and assess fetal liver injury in a rat model of acute pancreatitis in pregnancy (APIP) as well as its possible mechanisms and potential therapeutic targets. The APIP model was induced by sodium taurocholate in Sprague-Dawley rats during the third trimester. ISO-1, a macrophage migration inhibitory factor (MIF) antagonist, was given before the induction of APIP. In addition, sham-operated rats at later gestation were set as controls. Histological changes in the fetal liver and maternal pancreas were assessed. Amylase and lipase activity as well as the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were examined. The expression of MIF in fetal liver was determined by immunochemistry and the expression of NF-κB, IκBα, high mobility group box-1 protein (HMGB1), TNF-α, and IL-1β in fetal liver was determined by Western blot analysis. Ultrastructures of hepatic cells in fetal rats were observed under transmission electron microscopy. ISO-1 ameliorated the following: (i) pathological injuries in maternal pancreas and fetal liver; (ii) levels of TNF-α and IL-1β in maternal serum; and (iii) levels of MIF, myeloperoxidase, NF-κB, HMGB1, TNF-α, and IL-1β in fetal liver. Pathological damage and an inflammatory response in fetal liver were induced by APIP, and MIF inhibition ameliorated fetal liver injury by inhibiting the inflammatory cascade.