Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8648572 | Molecular Immunology | 2018 | 8 Pages |
Abstract
Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170â¯Î¼mol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (Pâ¯<â¯.05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H2O2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (Pâ¯<â¯.05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (Pâ¯<â¯.05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (Pâ¯<â¯.05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24â¯h after liver transplantation (Pâ¯<â¯.05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α
Keywords
MDAALTGSSGMCDSAMGSHJnkDBilHCCIRIROSIschaemia reperfusion injuryIschemia reperfusion injuryAlanine aminotransferaseALPAlkaline phosphataseS-adenosylmethionineDirect bilirubintumor necrosis factor-αTUNELTNF-αmalondialdehydeBile ductLiver transplantationHepatocellular carcinomahigh performance liquid chromatographyHPLCGlutathioneoxidized glutathioneReactive oxygen species
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Authors
Yong Tang, Hongpeng Chu, Guojun Cao, Xiaolong Du, Xiaobo Min, Chidan Wan,