Assessment of histological efficiency of clarithromycin, montelukast, and pentoxifylline treatments on experimental neonatal hyperoxic lung injury model

ASSESSMENT OF HISTOLOGICAL EFFICIENCY OF CLARITHROMYCIN,MONTELUKAST, AND PENTOXIFYLLINE TREATMENTS ONEXPERIMENTAL NEONATAL HYPEROXIC LUNG INJURY MODELSUMMARYObjective: Currently, there is no such treatment regimen which is demonstrated to beefficient in bronchopulmonary dysplasia. In this study, it is aimed to assess the efficiency ofclarithromycin, montelukast, and pentoxifylline treatments, alone and combinated, inreducing the hyperoxic lung injury at the histopathologic level.Material and Methods: The experiment was carried out in Experimental AnimalLaboratory, Dokuz Eylul University Medical School with total 47 newborn rat pups dividedto six groups during postnatal day 3 and 13. The rats belonging to group 1 were designated ascontrol group and kept in room air without exposure to hyperoxia. Group 2 (clarithromycin),3 (montelukast), 4 (pentoxifylline), 5 (clarithromycin + montelukast + pentoxifylline), and 6(plasebo) were kept in Plexiglas chamber and exposed to hyperoxia (%90 ± 2) throughout theexperiment. Alveolar surface area, fibrosis, and smooth muscle actin expression was assessedin the lungs, which were resected by thoracotomy on the postnatal day 14. One-way ANOVAtest was used for comparison of mean alveol area values, Kolmogorov-Smirnov analyses forcomparison of the ratio of fibrosis scores, and Kruskal-Wallis test together with MannWhitney-U test for the comparison of immunohistochemical scores.Results: Mean alveolar surface area (µm2) was found statistically significantly lower inthe group 6 rats with respect to group 1 (50.2 ± 10.4 and 65.3 ± 2.7, p=0.001). Drugtreatments, when used separately, were not detected superior to placebo regarding meanalveolar surface area. Combination treatment resulted in significantly higher mean lung areavalues with respect to placebo treatment group (64 ± 3 and 50.2 ± 10.4, p=0.002). Fibrosiswas found significantly high in the group 6 rats with respect to group 1 (p=0.007). Drugtreatments, when used separately or in combination, were not found statistically differentfrom placebo group regarding fibrosis. In consequence of immunohistochemical analyses, thesmooth muscle actin expression in the group 6 rats was detected significantly high withrespect to group 1 (Median actin score, 6 [0-12] ve 2 [1-4], p=0.045). Drug treatments, whenused separately, were not detected superior to placebo regarding smooth muscle actinexpression. Combination treatment resulted in significantly lower actin scores with respect toplacebo treatment group (Median actin score, 0 [0-1] ve 6 [0-12], p=0.005).3Conclusion: It is detected that clarithromycin, montelukast, and pentoxifyllinecombination treatment was superior to placebo treatment in the hyperoxic lung injury modelperformed on newborn rats. This study indicates that administration of drug combinationmight be successful in the new BPD, which has complex pathophysiologic processes andlacks established efficient treatment strategies.Key Words: Hyperoxic lung injury, bronchopulmonary dysplasia, newborn,clarithromycin, montelukast, pentoxifylline.4