Anti-inflammation effect of NecroX-7 with Mesenchymal Stem Cells(MSCs) in acute pancreatitis

Abstract

Background: Acute pancreatitis (AP) is known to be caused by various etiologies, such as heavy alcohol, gallstones, and cholelithiasis. AP rapidly damages surrounding tissue, acinar cells and leads to pancreatic inflammation and necrosis. In addition, it is a serious disease that easily leads to complications.[1,2] Variety of drugs for AP has been reported only a portion is used for the pharmacological treatment.[2-6] NecroX-7 (C25H32N4O4S2)is participated mitochondrial ROS and RNS inhibition of apoptosis on oxidative stress materials. Moreover, it is also known to have a cytoprotective and antioxidant effects on a variety of cell lines.[11-13] Mesenchymal stem cells (MSCs) have self-proliferation and differentiation capabilities of serve as a source of multipotent stem cells for various organs.[14-17] MSCs are also used previously in animal model of AP. Although, MSCs homing in damage process, induced inflammation of promoted the growth of stellate cells, the detailed mechanism has not been elaborated.[18-19] In the current study, we used NecroX-7 (NX-7) in combination with MSCs in animal model of AP. We investigated paracrine effect of NX-7 with MSCs infused on AP in results of improvement of anti-inflammation and anti-inflammation mechanism by analysis. Methods: Mice were fed the choline/methionine-deficient diet with 0.5% DL-ethionine (CDE) for 4 days. MSCs were transplantation via tail vein after 36 hours from the feeding diet. The blood samples were measurement after induction of pancreatitis for serum amylase and lipase levels. The paraffin-embedded tissues followed H&E staining and IHC staining by observation under a light microscope. Detection of MSCs was analyzed by RT-PCR. Results: Pancreas from NX-7 and NX-7 + MSCs infusion decreased edema, collapsed cell structure, and inflammatory cells compared with AP. Also, serum amylase and lipase levels decreased NX-7 and NX-7 + MSCs infusion. Furthermore, NX-7 and NX-7 + MSCs infusion significantly reduced expression levels of pro-inflammatory cytokines, but they increased anti-inflammatory cytokines. Moreover, MPO activity significantly increased AP. NX-7 and MSCs infusion were observed to decrease MPO activity than AP. AIFM1 was not observed in control, AP, and AP + NX-7, whereas that was detected MSCs infusion groups. Conclution: Consequently, signaling mechanism in AP is still not clearly revealed. NX-7 and MSCs infusion improved anti-inflammatory cytokines and suppressed pro-inflammatory cytokines. Also, that decreased serum amylase and lipase levels. Therefore, NX-7 and MSCs infusion had anti-inflammation effects and paracrine effect in AP. Furthermore, NX-7 assisted in homing of MSCs in an early stage of AP.