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.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome

“…[29] Moreover, Ji et al showed that rhEPO pretreatment inhibited NF-κB p65 and the release of proinflammatory cytokines. [14] Likewise, attenuation of cytokines was observed with rhEPO pretreatment in meconium-instilled rats in our study. Pulmonary inflammation is a key feature in the pathogenesis of MAS; therefore, the significant attenuation of inflammation with rhEPO pretreatment observed in this study may suggest the potential for use of EPO as a therapeutic agent in the prevention of lung damage from MAS.…”

“…[5] A growing body of evidence suggests that the protective role and potent anti-inflammatory activity of EPO, including inhibition of leukocyte infiltration and reduced levels of proinflammatory cytokines, has been reported in various in vivo studies. [3,[14][15][16][17][18][19] Ozer et al [21] showed that treatment of hyperoxia-exposed newborn rat pups with rhEPO significantly improved alveolar structure, and lessened fibrosis. Lee et al [3] also showed that rhEPO treatment significantly improved hyperoxia-induced lung damage.…”

“…[12,13] Accumulating evidence has demonstrated that EPO is beneficial in many diseases. [3,[14][15][16][17][18][19] For instance, EPO administration improved the tissue bioenergetics in a septic animal model. [19] Exogenous recombinant human EPO (rhEPO) reduced apoptosis in lipopolysaccharidetreated rats.…”

Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

“…The marine industry has been developing in recent years, and marine workers are prone to various open injuries [26]. Several previous studies have reported that SW immersion causes large amounts of inflammatory factors, such as IL-8, TNF, and NO, to be released from the injured area, causing multiple organ damage in the body and increasing the probability of disseminated intravascular coagulation, which ultimately leads to an increase in mortality [4,[27][28][29][30][31]. However, the effects of SW immersion on wound repair of full-thickness skin defects and its mechanism have not been reported in the literature.…”

Microbiota Composition and Pulmonary Surfactant Protein Expression as Markers of Death by Drowning

“…Because pulmonary surfactant‐associated protein levels can be elevated in tissue specimens, not only in drowned victims but also in cases of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), pulmonary surfactant protein A (SP‐A) can be useful as a marker of asphyxiation and ALI . ARDS/ALI is characterized by pulmonary edema and severe refractory hypoxemia, including drowning and asphyxia (hanging, suffocation, and aspiration) . Funayama et al and Zhu et al reported use of SP‐A immunohistochemical (IHC) staining in forensic pathology, as the IHC distribution of SP‐A is stable during decomposition.…”