Details

Autor(en) / Beteiligte

• Wu, Shu-Yu
• Tang, Shih-En
• Ko, Fu-Chang
• Wu, Geng-Chin
• Huang, Kun-Lun
• Chu, Shi-Jye

Titel

Valproic Acid Attenuates Acute Lung Injury Induced by Ischemia–Reperfusion in Rats

Ist Teil von

• Anesthesiology (Philadelphia), 2015-06, Vol.122 (6), p.1327-1337

Ort / Verlag

United States: Copyright by , the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND:Evidence reveals that histone deacetylase (HDAC) inhibition has potential for the treatment of inflammatory diseases. The protective effect of HDAC inhibition involves multiple mechanisms. Heme oxygenase-1 (HO-1) is protective in lung injury as a key regulator of antioxidant response. The authors examined whether HDAC inhibition provided protection against ischemia–reperfusion (I/R) lung injury in rats by up-regulating HO-1 activity. METHODS:Acute lung injury was induced by producing 40 min of ischemia followed by 60 min of reperfusion in isolated perfused rat lungs. The rats were randomly allotted to control group, I/R group, or I/R + valproic acid (VPA) group with or without an HO-1 activity inhibitor (zinc protoporphyrin IX) (n = 6 per group). RESULTS:I/R caused significant increases in the lung edema, pulmonary arterial pressure, lung injury scores, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 concentrations in bronchoalveolar lavage fluid. Malondialdehyde levels, carbonyl contents, and myeloperoxidase-positive cells in lung tissue were also significantly increased. I/R stimulated the degradation of inhibitor of nuclear factor-κB-α, nuclear translocation of nuclear factor-κB, and up-regulation of HO-1 activity. Furthermore, I/R decreased B-cell lymphoma-2, heat shock protein 70, acetylated histone H3 protein expression, and increased the caspase-3 activity in the rat lungs. In contrast, VPA treatment significantly attenuated all the parameters of lung injury, oxidative stress, apoptosis, and inflammation. In addition, VPA treatment also enhanced HO-1 activity. Treatment with zinc protoporphyrin IX blocked the protective effect of VPA. CONCLUSIONS:VPA protected against I/R-induced lung injury. The protective mechanism may be partly due to enhanced HO-1 activity following HDAC inhibition.