Protection against reperfusion lung injury via aborgating multiple signaling cascades by trichostatin A

• TSA is a histone deacetylase inhibitor with anti-inflammatory effects.
• TSA mitigated ischemia-reperfusion-induced lung injury
• TSA exert its anti-inflammatory effects through multiple biological pathways
• TSA may be a promising treatment for ischemia-reperfusion-induced lung injury

Trichostatin A (TSA) is a histone deacetylase inhibitor with anti-inflammatory effects. Nonetheless, little information is available about the effect of TSA in ischemia-reperfusion (IR)-induced lung injury. In a perfused rat lung model, IR was induced by 40 min of ischemia followed by 60 min of reperfusion. The rat lungs were randomly divided into several groups including control, control + TSA (0.1 mg/kg), IR, and IR + various dosages of TSA (0.05, 0.075, 0.1 mg/kg). Bronchoalveolar lavage fluids and lung tissues were obtained and examined at the end of the experiment. TSA dose-dependently diminished IR-induced increased vascular permeability and edema, pulmonary artery pressure, and histological changes in the lungs. Additionally, TSA suppressed lavage tumor necrosis factor-α and cytokine-induced neutrophil chemoattractant concentrations, cell infiltration, and myeloperoxidase-positive cells in the lung tissue. Furthermore, TSA attenuated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, degradation of the inhibitor of nuclear factor (NF)-κB, and nuclear NF-κB levels. TSA also decreased poly (ADP-ribose) polymerase but enhanced acetylated histone H3 acetylation, Bcl-2, and mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in IR lung tissue. Therefore, TSA exerted a protective effect on IR-induced lung injury via increasing histone acetylation and MKP-1 protein expression, repressing NF-κB, mitogen-activated protein kinase, and apoptosis signaling pathways.