Abstract
Introduction and AimMangafodipir 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.MethodsMice 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.ResultsMangafodipir 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.ConclusionsMangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.
Highlights
Introduction and AimMangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties
In addition to the known capability of fodipir to increase GSH levels under a variety of oxidative conditions [24,25,26], we have shown that mangafodipir displays pleiotropic antioxidant properties
Compared to the untreated ninety minutes’ ischemia control group, aspartate aminotransferase (ASAT) activities were significantly lower after administration of mangafodipir and intermittent clamping (IC) (P,0.01 and p = 0.01, respectively), and not significantly different from the basal level observed in the sham-operated group
Summary
Introduction and AimMangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. The common drawback of clamping is hepatic ischemia-reperfusion (I/R) injury, especially when the liver is affected by chronic hepatitis or cirrhosis, with a risk of poor postoperative outcome [4]. Two surgical strategies have been developed to minimize I/R injuries: intermittent clamping (IC) and ischemic preconditioning (IP). IC consists of an intermittent inflow occlusion followed by short periods of reperfusion and has demonstrated a protective effect [5,6,7]. IP has demonstrated a protective effect during liver resection in humans [9]. Studies in animal models of ischemia reperfusion have suggested that the protective effect of IP is mediated by an enhancement in endogeneous anti-oxidative stress mechanisms [10,11]
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