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Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats

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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.

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ACKNOWLEDGMENTS

The study was supported by grants (YYZD2014001) from the Jinling hospital.

The authors have no potential conflicts of interest to disclose.

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    Authors and Affiliations

    1. Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China

      Mu-huo Ji, Jian-hua Tong, Yuan-hui Tan, Wei-yan Li, Jian-jun Yang & Si-hai Zhu

    2. Department of Critical Care Medicine, No. 413 Hospital, Zhoushan, Zhejiang, China

      Zhen-yu Cao & Cong-yang Ou

    3. Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA

      Y. G. Peng

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    1. Mu-huo Ji
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    Correspondence to Si-hai Zhu.

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    This study was approved by the Ethics Committee of Jinling Hospital, Nanjing University and was performed in accordance with the Guide for the Care and Use of Laboratory Animals from the National Institutes of Health.

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    Mu-huo Ji and Jian-hua Tong contributed equally to this manuscript.

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    Ji, Mh., Tong, Jh., Tan, Yh. et al. Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats. Inflammation 39, 447–456 (2016). https://doi.org/10.1007/s10753-015-0268-0

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