We recently demonstrated the inhalation of
hydrogen gas, a novel medical therapeutic gas, ameliorates
ventilator-induced lung injury (VILI); however, the molecular mechanisms by which
hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled
hydrogen gas modulates the
nuclear factor-kappa B (NFκB) signaling pathway. VILI was generated in male C57BL6 mice by performing a
tracheostomy and placing the mice on a
mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without
positive end-expiratory pressure). The
ventilator delivered either 2%
nitrogen or 2%
hydrogen in balanced air. NFκB activation, as indicated by NFκB
DNA binding, was detected by electrophoretic mobility shift assays and
enzyme-linked
immunosorbent assay.
Hydrogen gas inhalation increased NFκB
DNA binding after 1h of ventilation and decreased NFκB
DNA binding after 2h of ventilation, as compared with controls. The early activation of NFκB during
hydrogen treatment was correlated with elevated levels of the antiapoptotic
protein Bcl-2 and decreased levels of Bax.
Hydrogen inhalation increased
oxygen tension, decreased lung
edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NFκB activation using SN50 reversed these protective effects. NFκB activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of
hydrogen against apoptotic and inflammatory signaling pathway activation during VILI.