Protective role of peroxisome proliferator-activated receptor β/δ in acute lung injury induced by prolonged hyperbaric hyperoxia in rats

•PPAR-β/δ activation has a protective role against lung injury induced by HBO2.•GW0742 decreases inflammatory mediators and apoptosis in lungs after HBO2 exposure.•GW0742 elevates antioxidant enzyme activities after HBO2 exposure.•GW0742 reduces NF-κB activation and ERK1/2 phosphorylation after HBO2 exposure.

Peroxisome proliferator-activated receptor (PPAR)-β/δ is a transcription factor that belongs to the PPAR family, but the role of PPAR-β/δ in acute lung injury (ALI) induced by hyperbaric oxygen is unknown. In this study we investigated if PPAR-β/δ activation protects from hyperoxia-induced ALI in a rat model. ALI was induced by prolonged hyperbaric oxygen (HBO2) (2.3 ATA, 100% O2) for 8 h. Administration of PPAR-β/δ agonist GW0742 (0.3 mg/kg, i.p.) at 1 and 6 h prior to HBO2 exposure significantly reduced the (1) lung injury, (2) proinflammatory cytokines (TNF-α, IL-1β, IL-6), (3) apoptosis (Bax/Bcl-2, cleaved-caspase-3 and TUNEL), (4) nuclear factor (NF)-κB expression level and DNA binding activity in the nucleus, and (5) extracellular signal-regulated kinase (ERK)1/2 phosphorylation and markedly elevated (6) superoxide dismutase and glutathione peroxidase activities as well as (7) IκB expression. However, administration of the PPAR-β/δ antagonist GSK0660 abolished these protective effects. These findings indicate that activation of PPAR-β/δ ameliorates hyperoxia-induced ALI in rats by up-regulating antioxidant enzyme activity as well as suppressing inflammation and apoptosis.