Molecular hydrogen provides protective effects against acute pancreatitis by inhibiting MAPK phosphorylation (ERK, JNK, p38) and NF-κB activation while upregulating Hsc70 expression, thereby reducing inflammatory mediator production (TNF-α and IL-1β). These findings elucidate the molecular mechanism by which hydrogen therapy ameliorates pancreatic inflammation and suggest potential therapeutic applications for acute pancreatitis management.
Plain-Language Summary
This study investigated how molecular hydrogen protects the pancreas during acute pancreatitis (sudden pancreatic inflammation). Researchers used laboratory cell cultures and animal models to identify which proteins and cellular pathways hydrogen affects. They found that hydrogen reduces inflammation by blocking certain signaling pathways (called MAPK and NF-κB) that trigger inflammatory molecules, while also increasing production of a protective protein called Hsc70.
Abstract
Molecular hydrogen (H2 ) 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 H2 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 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAPK; the activation of NF-κB and the expression of TNF-α and IL-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 H2 administration. The animal experiment results were consistent with those of the in vitro experiments. in conclusion, H2 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. This article is protected by copyright. All rights reserved.
DOI: 10.1111/febs.13629
