Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis.
OBJECTIVE
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-alpha, 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-alpha (TNF-alpha) 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.


CONCLUSIONS
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.
Tascilar
Oge
O
Department of Surgery, School of Medicine, Zonguldak Karaelmas Universitesi, Arastirma ve Uygulama Hastanesi Bashekimligi, Kozlu-Zonguldak 67600, Turkey.
Cakmak
Güldeniz Karadeniz
GK
Tekin
Ishak Ozel
IO
Emre
Ali Ugur
AU
Ucan
Bulent Hamdi
BH
Bahadir
Burak
B
Acikgoz
Serefden
S
Irkorucu
Oktay
O
Karakaya
Kemal
K
Balbaloglu
Hakan
H
Kertis
Gurkan
G
Ankarali
Handan
H
Comert
Mustafa
M
D000681:Amylases / Q000097:blood; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000150:complications*; D010996:Pleural Effusion; D011650:Pulmonary Alveoli / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D013657:Taurodeoxycholic Acid
D007376:Interleukin-2; D015850:Interleukin-6; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D004921:Erythropoietin; D008315:Malondialdehyde; D013657:Taurodeoxycholic Acid; D000681:Amylases