The effects of bosentan on hyperoxia-induced lung injury in neonatal rats.
Actins
/ biosynthesis
Animals
Animals, Newborn
Biomarkers
/ metabolism
Bosentan
/ administration & dosage
Disease Models, Animal
Endothelin Receptor Antagonists
/ administration & dosage
Hyperoxia
/ complications
Immunohistochemistry
Injections, Intraperitoneal
Lung
/ metabolism
Lung Injury
/ drug therapy
Rats
Rats, Wistar
Treatment Outcome
bosentan
hyperoxia-induced lung injury
treatment
Journal
Pediatrics international : official journal of the Japan Pediatric Society
ISSN: 1442-200X
Titre abrégé: Pediatr Int
Pays: Australia
ID NLM: 100886002
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
18
10
2018
revised:
14
05
2019
accepted:
21
06
2019
pubmed:
29
9
2019
medline:
6
5
2020
entrez:
28
9
2019
Statut:
ppublish
Résumé
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. 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). 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). This experimental study showed that bosentan had a protective effect on hyperoxic lung injury through its anti-inflammatory properties.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
This experimental study showed that bosentan had a protective effect on hyperoxic lung injury through its anti-inflammatory properties.
Substances chimiques
Actins
0
Biomarkers
0
Endothelin Receptor Antagonists
0
smooth muscle actin, rat
0
Bosentan
Q326023R30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1120-1126Subventions
Organisme : Pamukkale University Research Fund
ID : 2017TPF012
Informations de copyright
© 2019 Japan Pediatric Society.
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