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Updated: May 2, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
5'-Methylthioadenosine attenuates ischemia reperfusion injury after liver transplantation in rats
Yong Tang1, Weikang Zhang, Yu Zhang
1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, China.
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.
Insights
5'-Methylthioadenosine (MTA) reduces liver damage after transplantation by suppressing inflammation. This nucleoside inhibits key inflammatory pathways, including nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), improving liver function and reducing injury.
Area of Science:
- Immunology
- Hepatology
- Pharmacology
Background:
- 5'-Methylthioadenosine (MTA) is a nucleoside involved in polyamine synthesis.
- Previous research suggests MTA modulates inflammatory mediators via NF-κB and MAPK signaling pathways.
Purpose of the Study:
- To investigate the anti-inflammatory effects of MTA in a rat liver transplantation model.
- To determine if MTA can mitigate hepatic ischemia-reperfusion injury (IRI).
Main Methods:
- Orthotopic liver transplantation performed on Sprague Dawley rats.
- Rats received MTA (96 μmol/kg) or saline 30 minutes before surgery.
- Liver function (ALT, AST), inflammatory markers (TNF-α), and signaling pathway activation (NF-κB, MAPK) were assessed post-reperfusion.
Main Results:
- MTA pretreatment significantly improved liver function and attenuated hepatic IRI.
- MTA downregulated TNF-α levels and suppressed inflammatory responses.
- MTA inhibited IκBα degradation, NF-κB transcriptional activity, and MAPK activation.
Conclusions:
- MTA demonstrates significant protective effects against hepatic IRI following liver transplantation.
- The anti-inflammatory mechanism of MTA involves the inhibition of NF-κB and MAPK signaling pathways.
