title: Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats.
abstract: Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1β, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Tan
authors.affiliation: Department of Critical Care Medicine, No. 413 Hospital, Zhoushan, Zhejiang, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Cao
authors.affiliation: Department of Critical Care Medicine, No. 413 Hospital, Zhoushan, Zhejiang, China.
authors.forename: Cong-Yang
authors.initials: CY
authors.lastname: Ou
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Y G
authors.initials: YG
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China. liweiyan1965@126.com.
authors.forename: Si-Hai
authors.initials: SH
authors.lastname: Zhu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001784:Blood Gas Analysis; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004332:Drowning / Q000473:pathology*; D004921:Erythropoietin / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012623:Seawater / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D016753:Interleukin-10; D008315:Malondialdehyde; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D053148:Caspase 3; D010100:Oxygen
keywords: acute lung injury; cytokines; erythropoietin; reactive oxygen species; seawater