Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress

Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. In this study, we examined if the hydrogen could inhibit inflammation in a mouse model of collagen-induced arthritis (CIA) via oxidative stress on RA-FLSs. Moreover, to identify the mechanisms of action, we evaluated the effect of hydrogen on RA-FLSs development and the expression of pro-inflammatory cytokines and signaling pathways. Based on our result, H₂ enriched medium can increase super oxide dismutase (SOD) level following H₂O₂ treatment and decrease 8-hydroxy-2'-deoxyguanosine (8-OHdG) level. Since H₂O₂ treatment activates MAPK, NF-κB and TGF-β1 in cells, our study suggested that H₂ could inhibit H₂O₂ activated MAPK and NF-κB activation as well as TGF-β1 expression in treated cells. Taken together, our data suggested that H₂ can directly neutralize OH and ONOO^- to reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by H₂O₂ in RA-FLSs. H₂ can provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.