Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

Abstract

RESULTS:The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-α (TNF-α) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h. C O N C L U S I O N : E P O a d m i n i s t r a t i o n l e a d s t o asignificant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI. INTRODUCTIONAcute pancreatitis (AP) is a life-threatening necroinflammatory disease with significant morbidity and mortality rates, especially when complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure (MODS) [1,2] . Death occurs in 60% of the patients within the first 6 d of disease onset and pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) Abstract AIM: To investigate the effect of exogenous erythropoietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholateinduced acute necrotizing pancreatitis (ANP). BASIC RESEARCH METHODS:Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-α, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

“…In agreement with this notion, previous studies have demonstrated that EPO attenuated pulmonary neutrophil accumulation in animals experiencing hyperoxic injury [30,31], ischaemia/reperfusion injury [33,34], endotoxemia [36,37], nonseptic shock [38], and acute necrotizing pancreatitis [32]. Markers of neutrophil infiltration such as malondialdehyde levels and myeloperoxidase activity in the lung tissue are also reduced as a result of EPO administration [30,32,37].…”

“…EPO appears to protect the integrity of the pulmonary epithelial and endothelial cells and to attenuate the associated pulmonary oedema and deterioration of pulmonary oxygenation function. Treatment with EPO has been proven beneficial in experimental ALI caused by hyperoxia [30,31], acute necrotizing pancreatitis [32], ischaemia/reperfusion [33,34], experimental sepsis induced by cecal ligation and puncture [35] or LPS [36][37], zymosan induced nonseptic shock [38] and tracheobronchial and pulmonary type II epithelial injury, following traumatic brain injury [39]. In these studies EPO has been found to interact with its receptor (EPO-R) to induce a range of pleiotropic cytoprotective actions.…”

“…Markers of neutrophil infiltration such as malondialdehyde levels and myeloperoxidase activity in the lung tissue are also reduced as a result of EPO administration [30,32,37]. Leukocyte adhesion ligands such as P-selectin and intercellular adhesion molecule-1 (ICAM-1) are implicated in the activation of endothelial cells and the adhesion and migration of leukocytes to the sites of inflammation during lung injury [62].…”

“…In several experimental models of ALI, administration of EPO attenuated the accumulation in circulation, BAL and lung tissue of various cytokines, such as TNF-α, IL-6 and IL-1β [30,32,33,56,34,37]. Furthermore, in an experimental model of ischaemia/reperfusion ALI, pretreatment with EPO also reduced the over-expression of matrix metalloproteinase (MMP)-9 in lung tissue [34], which is considered to be an important factor correlated with the elevation of proinflammatory cytokines and microvascular permeability [67].…”

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

“…We report here that a single injection of pHBSP given intravenously to rats after the onset of resuscitation attenuated the renal dysfunction, liver injury, pancreatic injury and neuromuscular injury caused by severe HR in the anesthetized rat. There is evidence that EPO attenuates the degree of lung inflammation and injury caused by hyperoxic injury (20), ischemia-reperfusion (21) and acute necrotizing pancreatitis (22). We report here that pHBSP attenuated the degree of inflammatory cell infiltration, alveolar septal thickening and congestion in the lungs of rats subjected to HR.…”