Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2007; 13(46): 6172-6182
Published online Dec 14, 2007. doi: 10.3748/wjg.v13.i46.6172
Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis
Oge Tascilar, Güldeniz Karadeniz Cakmak, Ishak Ozel Tekin, Ali Ugur Emre, Bulent Hamdi Ucan, Burak Bahadir, Serefden Acikgoz, Oktay Irkorucu, Kemal Karakaya, Hakan Balbaloglu, Gürkan Kertis, Handan Ankarali, Mustafa Comert
Oge Tascilar, Güldeniz Karadeniz Cakmak, Ali Ugur Emre, Bulent Hamdi Ucan, Oktay Irkorucu, Kemal Karakaya, Hakan Balbaloglu, Mustafa Comert, Department of Surgery, Zonguldak Karaelmas University, School of Medicine, Kozlu-Zonguldak 67600, Turkey
Ishak Ozel Tekin, Department of Immunology, Zonguldak Karaelmas University, School of Medicine, Kozlu-Zonguldak 67600, Turkey
Burak Bahadir, Gürkan Kertis, Department of Pathology, Zonguldak Karaelmas University, The School of Medicine, Kozlu-Zonguldak 67600, Turkey
Serefden Acikgoz, Department of Biochemistry, Zonguldak Karaelmas University, School of Medicine, Kozlu-Zonguldak 67600, Turkey
Handan Ankarali, Department of Biostatistics, Zonguldak Karaelmas University, School of Medicine, Kozlu-Zonguldak 67600, Turkey
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Güldeniz Karadeniz Cakmak, Zonguldak Karaelmas Universitesi, Arastirma ve Uygulama Hastanesi Bashekimligi, Kozlu-Zonguldak 67600, Turkey. gkkaradeniz@yahoo.com
Telephone: +90-372-2610169 Fax: +90-372-2610155
Received: August 1, 2007
Revised: September 16, 2007
Accepted: October 6, 2007
Published online: December 14, 2007
Abstract

AIM: To investigate the effect of exogenous erythro-poietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate-induced acute necrotizing pancreatitis (ANP).

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.

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.

CONCLUSION: EPO administration leads to a significant 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.

Keywords: Erythropoietin; Acute pancreatitis; Acute lung injury; Acute respiratory distress syndrome; Cytokine