Abstract
Hepatic fibrosis is a chronic disorder caused by viral infection and/or metabolic, genetic and cholestatic disorders. A noninvasive procedure that enables the detection of liver fibrosis based on redox status would be useful for disease identification and monitoring, and the development of treatments. However, an appropriate technique has not been reported. This study describes a novel method for assessing the redox status of the liver using in vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) with the nitroxyl radical carbamoyl-PROXYL as a molecular imaging probe, which was tested in dimethylnitrosamine-treated mice as a model of liver fibrosis. Based on the pharmacokinetics of carbamoyl-PROXYL in control livers, reduction rate mapping was performed in fibrotic livers. Reduction rate maps demonstrated a clear difference between the redox status of control and fibrotic livers according to the expression of antioxidants. These findings indicate that in vivo DNP-MRI with a nitroxyl radical probe enables noninvasive detection of changes in liver redox status.
Highlights
The redox status, which is the balance between oxidant and antioxidant agents is a key pathophysiologic factor in numerous liver disorders[16,17]
The redox reaction is modulated by nitroxyl radicals, and the reduction rate depends on the redox environment, which is influenced by factors such as over-production of Reactive oxygen species (ROS) and reduced antioxidant levels
To demonstrate the feasibility of in vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) for liver fibrosis, surface coils were constructed for highly sensitive local imaging (Fig. 1a)
Summary
The redox status, which is the balance between oxidant and antioxidant agents is a key pathophysiologic factor in numerous liver disorders[16,17]. Reactive oxygen species (ROS) play a critical role in the initiation of fibrosis by stimulating the release of profibrogenic growth factors, and cytokines[18,19]. This occurs independently of TGF-ß, a redox-sensitive gene, and free radicals lead to increased TGF-ß expression in hepatic stellate cells, which activates collagen-producing cells. The objective of this study was to evaluate the redox status in liver fibrosis using in vivo DNP-MRI with nitroxyl radicals as molecular imaging probes, and to apply this method to a dimethylnitrosamine (DMN)-treated animal model
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