Examination of progression to mice steatohepatitis focusing on the detection of reactive oxygen species using MRI

<p>[Background and Aim] Drug-induced steatosis has a risk to progress to steatohepatitis, cirrhosis or cancer, and there are no effective means for noninvasively monitoring the progression of this lesion. Reactive oxygen species (ROS) are thought to be involved in the progression of this lesion. In resent years, in preclinical studies by electron spin resonance using nitroxyl radical as probe, the decay rate of signal intensity in ROS target organs / tissues was reported to have increased. Therefore, we examined the change of the decay rate with the progression of steatohepatitis in mice using MRI, which is similar magnetic resonance method and widely used clinically, and investigates the utilization of decay rate as steatohepatitis biomarker and the involvement of ROS.</p><p>[Materials and Methods] Five or 8-week-old NASH model mice (STAM^TMmice) were subjected to in vivo MRI. 3-Carbamoyl-PROXYL (CmP), which is one of the nitroxyl radical, was dosed intravenously 2 minutes after starting data acquisition and images were acquired for 17 minutes at 10 second intervals. Decay rate was calculated over time by signal intensity at liver. Histopathological examination at liver was conducted after MRI measurements. C57BL/6J mice as control were treated similarly.</p><p>[Results and Discussion] Since decay rate at liver increased according to the progression of steatohepatitis, ROS was considered to be involved in the progression of steatohepatitis. It was speculated that progression of drug-induced steatosis could be monitored noninvasively by using this method.</p>