title: 5'-Methylthioadenosine attenuates ischemia reperfusion injury after liver transplantation in rats.
abstract: 5'-Methylthioadenosine (MTA) is a nucleoside generated from S-adenosylmethionine (SAM) during polyamine synthesis. Previous study has indicated that MTA regulated the production of inflammatory mediators by modulating the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signal pathway. The objective of this study was to determine whether MTA possessed anti-inflammatory properties during rat liver transplantation. Sprague Dawley (SD) to SD rat orthotropic liver transplantation was performed according to the Kamada's technique. Donors in MTA group were given a single dose of MTA (96 μmol/kg, intraperitoneal) 30 min before surgery (n = 36), and the control group were given the same volume of normal saline (n = 36) intraperitoneally. The histopathologic change in the liver was analyzed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), inhibitors of kappa B alpha (IκBα) degradation, NF-κB transcriptional activity, and MAPK activation were determined at 3, 6, and 24 h after reperfusion. Pretreatment with MTA significantly improved liver function, attenuated hepatic ischemia-reperfusion injury (IRI) by downregulating TNF-α level and suppressing inflammatory reaction after liver transplantation. Moreover, MTA also inhibited the IκBα degradation, NF-κB transcriptional activity, and the activation of MAPK signal. MTA protected against hepatic IRI by suppressing inflammatory reaction following liver transplantation. The mechanism for this effect of MTA is mediated, at least in part, by inhibiting the activation of NF-κB and MAPK signal pathway.
authors.affiliation: Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Weikang
authors.initials: W
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Yan
authors.forename: Chidan
authors.initials: C
authors.lastname: Wan
mesh_terms: D000818:Animals; D003839:Deoxyadenosines / Q000494:pharmacology / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D013872:Thionucleosides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D003839:Deoxyadenosines; D016328:NF-kappa B; D013872:Thionucleosides; C008500:5'-methylthioadenosine