Rebamipide attenuates LPS-induced acute lung injury in rats via modulation of macrophage polarization, PDE4B/cAMP/PKA/p-CREB and NF-κB signaling

Acute lung injury (ALI) is a severe, potentially fatal condition associated with respiratory failure and high mortality, with limited effective therapeutic options. Rebamipide (REB), a gastroprotective agent with reported antioxidant and anti-inflammatory properties, has not been fully investigated in ALI. This study aimed to evaluate the effects and underlying mechanisms of REB in a lipopolysaccharide (LPS)-induced ALI rat model. Twenty-four Sprague–Dawley rats were randomly divided into four groups: control, REB (100 mg/kg orally for 10 days), LPS (5 mg/kg intraperitoneally on day 10), and REB + LPS (REB pretreatment for 10 days followed by LPS injection on day 10). REB administration attenuated LPS-induced pulmonary oxidative stress and inflammatory responses, as evidenced by reduced pro-inflammatory cytokines and improved antioxidant status. Additionally, REB modulated macrophage polarization markers and downregulated PDE4B expression. These changes were associated with increased cAMP, PKA, and p-CREB levels, along with inhibition of NF-κB p65 activation in lung tissue. In conclusion, REB exerts protective effects against LPS-induced ALI through modulation of inflammatory and oxidative stress pathways involving the PDE4B/cAMP/PKA/p-CREB axis and NF-κB signaling. These findings suggest that REB may represent a promising candidate for further investigation in inflammatory lung disorders.

Schematic diagram for protective mechanisms of REB against lipopolysaccharide-induced acute lung injury.