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The effects of bosentan on hyperoxia‐induced lung injury in neonatal rats
Author(s) -
Özdemir Özmert MA,
Taban Özgün,
Enli Yaşar,
Bir Ferda,
Şahin Barbaros,
Ergin Hacer
Publication year - 2019
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.14013
Subject(s) - medicine , bosentan , bronchopulmonary dysplasia , endothelin receptor , fibrosis , gastroenterology , endothelin receptor antagonist , pregnancy , receptor , gestational age , biology , genetics
Background Bronchopulmonary dysplasia (BPD) remains an important cause of morbidity and mortality in premature infants. There is currently no proven effective treatment modality for BPD, and inflammation and oxidative injury play an important role in the pathogenesis of this disease. This study investigated the histopathological and biochemical effects of bosentan, which is a non‐specific endothelin receptor antagonist with known antioxidant and anti‐inflammatory properties, on hyperoxia‐induced lung injury (HILI) in neonatal rats. Methods The experiment was performed on newborn rats from the 3rd to the 13th postnatal day. The rats were randomly divided into six groups: Group 1 (air‐exposed + saline, n = 6); Group 2 (HILI, n = 8); Group 3 (air‐exposed + bosentan, n = 7); Group 4 (HILI + saline, n = 7); Group 5 (HILI + early bosentan‐treated group, n = 6), and Group 6 (HILI + late bosentan‐treated group, n = 7). Bosentan was administered (30 mg/kg/day) intraperitoneally. The histopathological effects of bosentan on lung tissue were assessed by their alveolar surface area, fibrosis, and smooth muscle actin (SMA) scores, and the biochemical effects on lung tissue were assessed by interleukin‐1 beta (IL‐1β), IL‐6, IL‐10, and tumor necrosis factor‐alpha (TNF‐α). Results The alveolar surface area and fibrosis scores were found to be significantly higher in HILI groups compared with Group 1 ( P < 0.01). The SMA scores in HILI groups were also significantly higher than Group 1 ( P < 0.01). Bosentan treatment, especially late therapy, reduced all of these histopathological scores and the levels of IL‐6 and TNF‐α in the hyperoxia groups ( P < 0.01). Conclusion This experimental study showed that bosentan had a protective effect on hyperoxic lung injury through its anti‐inflammatory properties.