Shu-Yu Wu1, Shih-En Tang, Fu-Chang Ko, Geng-Chin Wu, Kun-Lun Huang, Shi-Jye Chu. 1. From Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China (S.-Y.W., K.-L.H.); Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China (S.-E.T., K.-L.H.); Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, Republic of China (F.-C.K., G.-C.W.); and Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China (S.-J.C.).
Abstract
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.
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.
Authors: Ben E Biesterveld; Ali Z Siddiqui; Rachel L O'Connell; Henriette Remmer; Aaron M Williams; Alizeh Shamshad; William M Smith; Michael T Kemp; Glenn K Wakam; Hasan B Alam Journal: J Surg Res Date: 2021-05-20 Impact factor: 2.417
Authors: Qifeng Zhao; Ji Wu; Zhiyong Lin; Qingwang Hua; Weixi Zhang; Leping Ye; Guowei Wu; Jie Du; Jie Xia; Maoping Chu; Xingti Hu Journal: Inflammation Date: 2016-08 Impact factor: 4.092