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Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
Mangafodipir protects against hepatic ischemia-reperfusion injury in mice
Romain Coriat1, Mahaut Leconte, Niloufar Kavian
1Laboratoire d'Immunologie, EA1833 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, AP-HP, Hôpital Cochin, Paris, France.
Introduction And Aim:
Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse.
Methods:
Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia.
Results:
Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning.
Conclusions:
Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.
Insights
Mangafodipir (MnDPDP) effectively prevents liver damage from ischemia-reperfusion injury in mice. This antioxidant agent demonstrated significant protection, improving survival rates and reducing tissue damage, similar to other protective methods.
Area of Science:
- Hepatology
- Pharmacology
- Surgical Research
Background:
- Reactive oxygen species contribute to ischemia-reperfusion (I/R) injuries.
- Mangafodipir (MnDPDP) is an MRI contrast agent with antioxidant properties.
- Investigating MnDPDP's potential to mitigate liver I/R injury is warranted.
Purpose of the Study:
- To evaluate the efficacy of mangafodipir in preventing hepatic ischemia-reperfusion injury in a mouse model.
- To compare mangafodipir's protective effects against ischemic preconditioning and intermittent inflow occlusion.
Main Methods:
- Mice underwent 90 minutes of 70% hepatic ischemia.
- Mangafodipir (10 mg/kg) or saline was administered 30 minutes pre-ischemia.
- Injury assessed via serum ASAT, histology, apoptosis markers, and survival rates.
Main Results:
- Mangafodipir significantly reduced serum ASAT activity and liver tissue damage (P<0.01).
- Hepatocyte apoptosis markers were decreased, and survival rates increased in mangafodipir-treated mice (P<0.001).
- Protection levels were comparable to intermittent inflow occlusion and superior to ischemic preconditioning.
Conclusions:
- Mangafodipir demonstrates significant protective effects against hepatic ischemia-reperfusion injury in mice.
- Its antioxidant properties suggest potential as a novel preventive therapeutic agent.
- Further research into mangafodipir for clinical application in I/R injury is recommended.

