Inhibition of macrophage migration inhibitory factor attenuates inflammation and fetal kidney injury in a rat model of acute pancreatitis in pregnancy.

Abstract

Acute pancreatitis in pregnancy (APIP) is a severe disease during pregnancy that mostly occurs during the third trimester. It can lead to additional complications including preterm delivery and high fetal mortality. In this study, we investigated the protective effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of macrophage migration inhibitory factor (MIF), on fetal kidney injury associated with the maternal acute necrotizing pancreatitis (ANP) and its potential mechanisms in a rat model. The APIP rat model was induced by retrograde infusion of sodium taurocholate saline solution into biliopancreatic duct. ISO-1 was given by intraperitoneally injection 30 min before the model was induced. The levels of maternal serum amylase, lipase, tumor necrosis factor-α (TNF-α) and interleukins (IL)-1β were measured. Maternal pancreas and fetal kidney injury were evaluated, and the expressions of MIF, phospho-p38MAPK (p-p38), nuclear factor-κB (NF-κB), TNF-α, IL-1β in fetal kidneys were detected. The results showed that fetal rats exhibited obvious acute kidney injury during APIP, and pregnant rats pretreated with ISO-1 notably attenuated the lesions. ISO-1 also significantly reduced the expression of MIF and the activations of p38MAPK, NF-κB, as well as the levels of TNF-α and IL-1β. These results indicated that ISO-1 could attenuate fetal kidney injury in pregnant rats with ANP by inhibiting MIF mediated p38MAPK/NF-κB signal pathways to reduce inflammatory response.

• Authors: Man Li, Jia Yu, Liang Zhao, Fang-Chao Mei, Yu Zhou, Yu-Pu Hong, Teng Zuo, Wei-Xing Wang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 68 Pg. 106-114 (Mar 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30622028 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• 3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
• Anti-Inflammatory Agents
• Interleukin-1beta
• Isoxazoles
• Macrophage Migration-Inhibitory Factors
• NF-kappa B
• Tumor Necrosis Factor-alpha
• p38 Mitogen-Activated Protein Kinases
• Intramolecular Oxidoreductases
• Mif protein, rat

Topics

• Acute Kidney Injury (drug therapy, metabolism, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Female
• Fetus
• Inflammation (drug therapy, metabolism, pathology)
• Interleukin-1beta (metabolism)
• Intramolecular Oxidoreductases (antagonists & inhibitors, immunology)
• Isoxazoles (pharmacology, therapeutic use)
• Kidney (metabolism, pathology, ultrastructure)
• Macrophage Migration-Inhibitory Factors (antagonists & inhibitors, immunology)
• NF-kappa B (metabolism)
• Pancreas (immunology, pathology)
• Pancreatitis, Acute Necrotizing (drug therapy, metabolism, pathology)
• Pregnancy
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)