Related Experiment Video
Updated: May 16, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat
Ismail Ben Mosbah1, Yann Mouchel, Julie Pajaud
1Inserm, UMR991, Foie, Métabolismes et Cancer, CHU Pontchaillou, Rennes, France.
Abstract:
Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation strategy holds great promise for translation to clinical liver transplantation.
Insights
Donor pretreatment with Mangafodipir trisodium (MnDPDP) protects rat liver grafts from ischemia/reperfusion injury. This novel organ preservation strategy reduces cell damage and improves graft function, showing promise for clinical liver transplantation.
Area of Science:
- Transplantation immunology
- Organ preservation science
- Hepatology
Background:
- Ischemia/reperfusion (I/R) injury is a major complication in liver transplantation, primarily caused by reactive oxygen species (ROS) generated during revascularization.
- Antioxidant enzyme delivery could mitigate ROS effects and enhance initial liver graft function.
- Mangafodipir trisodium (MnDPDP), an MRI contrast agent, possesses potent antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of donor pretreatment with MnDPDP against liver I/R injury.
- To evaluate MnDPDP's impact on liver graft function and integrity following cold preservation and ex vivo reperfusion.
Main Methods:
- Sprague Dawley rat livers were harvested after donor pretreatment with MnDPDP or vehicle.
- Livers underwent 24-hour cold preservation followed by 120-minute ex vivo reperfusion.
- Assessed parameters included ATP content, tissue integrity, cell injury markers, bile production, lipid peroxidation, mitochondrial damage, apoptosis, Nrf2/HIF-1α pathway activation, and nitric oxide (NO) production.
Main Results:
- MnDPDP pretreatment significantly increased ATP content post-preservation and enhanced ATP recovery after reperfusion.
- Treated livers exhibited improved tissue integrity, reduced hepatocellular and endothelial cell injury, and increased bile production.
- MnDPDP administration decreased lipid peroxidation, mitochondrial damage, and apoptosis, while activating Nrf2/HIF-1α pathways and modulating NO synthase expression.
Conclusions:
- Donor pretreatment with MnDPDP effectively protects rat liver grafts against cold I/R injury.
- This protective effect is linked to reduced oxidative stress, preserved mitochondrial function, and modulated inflammatory responses.
- MnDPDP represents a promising, clinically relevant strategy for enhancing organ preservation in liver transplantation.
