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Inflammation ; 39(1): 447-456, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26454446

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)-1ß, 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-1ß, 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.


Subject(s)
Acute Lung Injury/prevention & control , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Apoptosis/drug effects , Cytokines/metabolism , Drowning/pathology , Erythropoietin/therapeutic use , Oxidative Stress/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Animals , Blood Gas Analysis , Caspase 3/metabolism , Down-Regulation/drug effects , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lung/pathology , Male , Malondialdehyde/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Oxygen/blood , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Seawater/adverse effects , Superoxide Dismutase/metabolism , Tomography, X-Ray Computed , Tumor Necrosis Factor-alpha/metabolism
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