PMID- 26151294 OWN - NLM STAT- MEDLINE DCOM- 20160620 LR - 20181202 IS - 1521-0499 (Electronic) IS - 0190-2148 (Linking) VI - 41 IP - 7 DP - 2015 TI - Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved. PG - 404-14 LID - 10.3109/01902148.2015.1054053 [doi] AB - PURPOSE/AIM: Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. MATERIALS AND METHODS: We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. RESULTS: The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. CONCLUSIONS: This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway. FAU - Cao, Huifang AU - Cao H AD - a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China. FAU - Feng, Ying AU - Feng Y AD - b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China. FAU - Ning, Yunye AU - Ning Y AD - a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China. FAU - Zhang, Zinan AU - Zhang Z AD - b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China. FAU - Li, Weihao AU - Li W AD - b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China. FAU - Li, Qiang AU - Li Q AD - a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China. LA - eng PT - Journal Article PL - England TA - Exp Lung Res JT - Experimental lung research JID - 8004944 RN - 0 (Antioxidants) RN - 0 (Protoporphyrins) RN - 15442-64-5 (zinc protoporphyrin) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - S798V6YJRP (Edaravone) RN - T3CHA1B51H (Antipyrine) SB - IM MH - Acute Lung Injury/drug therapy/metabolism MH - Alveolar Epithelial Cells/*drug effects/metabolism MH - Animals MH - Antioxidants/metabolism MH - Antipyrine/*analogs & derivatives/pharmacology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Edaravone MH - Epithelial Cells/*drug effects/metabolism MH - Heme Oxygenase-1/*metabolism MH - Humans MH - Hyperoxia/*drug therapy/metabolism MH - Male MH - Oxidation-Reduction/drug effects MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Protoporphyrins/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Up-Regulation/drug effects OTO - NOTNLM OT - HO-1 OT - PI3K/Akt pathway OT - edaravone OT - hyperoxia OT - oxidative injury EDAT- 2015/07/08 06:00 MHDA- 2016/06/21 06:00 CRDT- 2015/07/08 06:00 PHST- 2015/07/08 06:00 [entrez] PHST- 2015/07/08 06:00 [pubmed] PHST- 2016/06/21 06:00 [medline] AID - 10.3109/01902148.2015.1054053 [doi] PST - ppublish SO - Exp Lung Res. 2015;41(7):404-14. doi: 10.3109/01902148.2015.1054053.