MAPK s and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis

Molecular hydrogen (H 2 ) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis ( AP ) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H 2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein–protein interaction networks of these proteins. The results triggered our interest in mitogen‐activated protein kinase ( MAPK ) and heat shock cognate 71 kD a protein (Hsc70). The subsequent in vitro experiments showed that H 2 treatment inhibited the phosphorylation of extracellular signal‐regulated kinase ( ERK ), c‐jun N‐terminal kinase ( JNK ), and p38 MAPK , and activated NF ‐κB and the expression of tumor necrosis factor α and interleukin‐1β, while simultaneously preventing the translocation of phospho‐ ERK , phospho‐ JNK , and phospho‐p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H 2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H 2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression.