Clarithromycin, montelukast, and pentoxifylline combination treatment ameliorates experimental neonatal hyperoxic lung injury.
OBJECTIVE
We aimed to assess the efficiency of clarithromycin, montelukast, and pentoxifylline treatments, alone and in combination, in reducing hyperoxic lung injury at the histopathologic level.


METHODS
The experiment was carried out with 47 newborn rat pups divided into six groups during postnatal days 3 to 13. The rats belonging to group 1 were designated as the control group and kept in room air without exposure to hyperoxia. Group 2 (clarithromycin), group 3 (montelukast), group 4 (pentoxifylline), group 5 (clarithromycin + montelukast + pentoxifylline combination), and group 6 (placebo) were kept in plexiglass chamber and exposed to hyperoxia (88-92%) throughout the experiment. Alveolar surface area percentage, fibrosis, and smooth muscle actin expression were assessed in the lungs, which were resected by thoracotomy on postnatal day 14.


RESULTS
Drug treatments, when used separately, were not detected to be superior to placebo with regard to mean alveolar surface area, fibrosis, and smooth muscle actin expression. Combination treatment resulted in significantly higher mean lung area percentages and lower actin scores with respect to the placebo treatment group (64.0% vs. 50.2%, p=0.002; 0 (0-1) vs. 7 (2-12), p=0.005, respectively).


CONCLUSIONS
It was determined that clarithromycin, montelukast, and pentoxifylline combination treatment is superior to placebo treatment in the newborn rat hyperoxic lung injury model. The present study indicates that combination therapy might be successful in bronchopulmonary dysplasia, which has complex pathophysiologic processes and lacks established efficient treatment strategies.
Department of Pediatrics, Medical Faculty, Dokuz Eylul University, Inciralti, Izmir, Turkey.
Korcan
K
Demir
Abdullah
A
Kumral
Nuray
N
Duman
Sulen
S
Sarioglu
Osman
O
Yilmaz
Didem Cemile
DC
Yesilirmak
Aydanur
A
Kargi
Hasan
H
Ozkan
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001997:Bronchopulmonary Dysplasia / Q000473:pathology / Q000517:prevention & control*; D017291:Clarithromycin / Q000627:therapeutic use*; D003521:Cyclopropanes; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D007231:Infant, Newborn; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects; D010431:Pentoxifylline / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D013440:Sulfides
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D017291:Clarithromycin; C093875:montelukast; D010431:Pentoxifylline