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Eur J Pediatr Surg 2020; 30(01): 071-078
DOI: 10.1055/s-0039-1697908
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Investigation of Bosentan's Effects on Pulmonary Contusion Created by Blunt Thoracic Trauma in Rats

Gonca Gercel 
1   Department of Pediatric Surgery, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
,
Burhan Aksu
1   Department of Pediatric Surgery, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
,
Seyma Ozkanli
2   Department of Pathology, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
,
Hafize Uzun
3   Department of Biochemistry, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
,
Feyza Aksu
4   Department of Cardiology, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
,
Erdem Ozatman
1   Department of Pediatric Surgery, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
,
Çiğdem Ulukaya Durakbaşa
1   Department of Pediatric Surgery, Istanbul Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
› Author Affiliations
Further Information

Publication History

13 May 2019

20 August 2019

Publication Date:
10 October 2019 (online)

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Abstract

Introduction Bosentan is an endothelin-1 receptor antagonist with anti-inflammatory, antioxidant, and antiproliferative effects. We aimed to evaluate its effects on lung tissue in a pulmonary contusion (PC) model.

Materials and Methods The rats were randomly divided into five groups: PC3: PC evaluated on the 3rd day (n = 8), PC-B3: PC enteral bosentan 100 mg/kg/day, for 3 days (n = 8), PC7: PC evaluated on the 7th day (n = 7), PC-B7: PC 7 days bosentan 100 mg/kg/day, for 7 days (n = 8), C: control (n = 6). Unilateral lung contusion was created by dropping a metal weight onto the chest. The rats were sacrificed on the 3rd or the 7th days. The lung tissue was evaluated histopathologically for alveolar edema, congestion, and leukocyte infiltration, biochemically for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels, and immunohistochemically for inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and apoptosis scores.

Results Alveolar edema, congestion, and leukocyte infiltration scores were increased in all groups compared with the control group (p < 0.05) and decreased in bosentan-treated groups compared with the relevant nontreated groups (p < 0.05). Fibrosis was observed only in PC7 and PC-B7 groups. Bosentan did not have any effect on fibrosis development. iNOS and eNOS levels were higher in all groups compared with the control (p < 0.05) without a difference in the nontreated versus treated groups (p > 0.05). Bosentan treatment caused decreased MDA and increased SOD levels in comparison to the nontreated groups (p < 0.05). Tissue NO levels did not show any significant difference among groups. PC groups had higher levels of apoptosis compared with the control group (p < 0.05). The degree of apoptosis decreased in bosentan-treated groups compared with the nontreated groups (p < 0.05).

Conclusion PC causes progressive lung tissue damage. Bosentan reduced leukocyte infiltration and alveolar edema and congestion caused by PC. It also decreased MDA levels and increased SOD levels. Bosentan prevents tissue damage by inhibiting acute inflammatory response and reduces oxidative stress secondary to inflammation. It has therapeutic effects on apoptosis.

Keywords

pulmonary contusion - experimental - bosentan - rat - blunt thoracic trauma
 

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