The protection mechanism of proline from D-galactosamine hepatitis involves the early activation of ROS-eliminating pathway in the liver

The oral pre-administration of proline, one on the non-essential amino acids, has been shown to effectively protect the liver from D-galactosamine (GalN)-induced liver injury and dramatically improve the survival rate. In the previous study, we reported that protective effect of proline involves the early activation of IL-6/STAT-3 pathway, an anti-inflammatory and regenerative signaling in the liver. Reactive oxygen species (ROS) are mediator of cellular injury and play an important role in hepatic damage during GalN-induced hepatitis. The aim of this study is to investigate the effect of proline on ROS-eliminating system. The activities of major ROS-detoxifying enzymes, i.e., glutathione peroxidase (GP), glutathione reductase (GR), catalase, and the level of glutathione in the liver were determined. Catalase activity was significantly upregulated in proline group from 0 to 3 h after GalN-injection, although GP and GR were downregulated during this period, compared with control group. From 6 to 12 h, the level of reduced glutathione (GSH) was significantly higher and the ratio of GSH/oxidized glutathione (GSSG) tended to be higher in proline group. Consistently with this, at 6 h, the GR activity in the proline group was significantly higher, followed with the higher tendency of GP activity at 12 h. Catalase activity was also significantly higher at 12 h. Taken together, catalase was activated at the beginning, followed with the significant activation of glutathione redox system around 6 to 12 h in proline group. These results suggest that the elimination of ROS in the liver was accelerated in proline group compared with control group at the very early stage of GalN-induced hepatitis.