title: 4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF-1α in seawater aspiration-induced lung injury in rats.
abstract: 4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats.
authors: Department of Pharmacological and Toxicological Research Centre, No. 210 Hospital of Chinese People's Liberation Army, Dalian 116021, China. lhw@wfmc.edu.cn.
authors: Zhongyang
authors: Z
authors: Liu
authors: Department of Pharmacological and Toxicological Research Centre, No. 210 Hospital of Chinese People's Liberation Army, Dalian 116021, China. yyyes@wfmc.edu.cn.
authors: Ronggang
authors: R
authors: Xi
authors: Department of Pharmacological and Toxicological Research Centre, No. 210 Hospital of Chinese People's Liberation Army, Dalian 116021, China. wangfei@wfmc.edu.cn.
authors: Zhiran
authors: Z
authors: Zhang
authors: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. wangdongrui@gmail.com.
authors: Wangping
authors: W
authors: Li
authors: Department of Pharmacological and Toxicological Research Centre, No. 210 Hospital of Chinese People's Liberation Army, Dalian 116021, China. shifuyan@wfmc.edu.cn.
authors: Yan
authors: Y
authors: Liu
authors: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. wangdongrui@gmail.com.
authors: Faguang
authors: F
authors: Jin
authors: Department of Pharmacological and Toxicological Research Centre, No. 210 Hospital of Chinese People's Liberation Army, Dalian 116021, China. liwanwei@wfmc.edu.cn.
authors: Xiaobo
authors: X
authors: Wang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology* / Q000627:therapeutic use; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053120:Respiratory Aspiration / Q000150:complications; D012623:Seawater; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010648:Phenylacetates; D042461:Vascular Endothelial Growth Factor A; C026246:4-hydroxyphenylacetate