Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury.
BACKGROUND
Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury.


METHODS
Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters.


RESULTS
SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3.


CONCLUSIONS
We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Guven
G
Kaya
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Mehmet
M
Saldir
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Adem
A
Polat
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
M Kursat
MK
Fidanci
b Pathology , Istanbul Medeniyet University, Goztepe Training and Research Hospital , Istanbul , Turkey.
Aysegul
A
Erdem
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Galip
G
Erdem
c Clinical Biochemistry , Gulhane Military School of Medicine , Ankara , Turkey.
Yasemin Gulcan
YG
Kurt
d Pediatrics, Division of Neonatology , Kanuni Sultan Süleyman Training and Research Hospital , Istanbul , Turkey.
Merih
M
Cetinkaya
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Ferhat
F
Cekmez
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Onder
O
Onguru
a Department of Pediatrics , Gulhane Military School of Medicine , Ankara , Turkey.
Turan
T
Tunc
D055371:Acute Lung Injury / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004195:Disease Models, Animal; D000068800:Etanercept / Q000494:pharmacology*; D018496:Hyperoxia / Q000150:complications*; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
TNF-alpha; bronchopulmonary dysplasia; etanercept; hyperoxy model; newborn