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
