Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury
<i>Objective</i>: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia–reperfusion (I/R) injury, with a focus on myocardial tissue involvement. <i>Methods</i>: Twenty-four male Wistar rats...
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MDPI AG
2025-07-01
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| author | Şevki Mustafa Demiröz Ayşegül Küçük Esra Tekin Sibel Söylemez Hanife Yılmaz Şaban Cem Sezen Muharrem Atlı Hüseyin Demirtaş Abdullah Özer Yusuf Ünal Mustafa Arslan |
| author_facet | Şevki Mustafa Demiröz Ayşegül Küçük Esra Tekin Sibel Söylemez Hanife Yılmaz Şaban Cem Sezen Muharrem Atlı Hüseyin Demirtaş Abdullah Özer Yusuf Ünal Mustafa Arslan |
| author_sort | Şevki Mustafa Demiröz |
| collection | DOAJ |
| description | <i>Objective</i>: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia–reperfusion (I/R) injury, with a focus on myocardial tissue involvement. <i>Methods</i>: Twenty-four male Wistar rats were randomly assigned to four groups: sham, bosentan, I/R, and I/R + bosentan. Lung I/R injury was induced by hilar clamping for 45 min, followed by 60 min of reperfusion. Bosentan (30 mg/kg) was administered intraperitoneally 30 min prior to the procedure. Myocardial tissue was evaluated histopathologically for structural disorganization, inflammation, fibrosis, and edema. TGF-β1 protein levels in myocardial tissue were compared across the groups using β-actin as the loading control. ELISA was used to quantify ET-1, NF-κB, and p53 levels, while spectrophotometric analysis was employed to assess MDA levels and the activities of SOD and CAT enzymes in heart tissue. <i>Results</i>: The I/R group exhibited significant myocardial disorganization, inflammation, and interstitial edema compared to the sham and bosentan groups. Bosentan treatment markedly ameliorated these histopathological alterations. Additionally, the I/R group showed elevated levels of ET-1, NF-κB, p53, and MDA, along with reduced SOD and CAT activities; these changes were significantly attenuated by bosentan administration. Bosentan treatment significantly reduced myocardial ET-1 levels (from 136.88 ± 5.02 to 120.18 ± 2.67 nmol/g, <i>p</i> = 0.003), NF-κB levels (from 0.87 ± 0.04 to 0.51 ± 0.03 ng/mg, <i>p</i> = 0.002), and TGF-β1 expression (from 1.72 ± 0.10 to 0.91 ± 0.08 relative units, <i>p</i> = 0.001). Moreover, bosentan increased antioxidant enzyme activities, elevating SOD levels from 21.45 ± 1.23 to 32.67 ± 1.45 U/mg protein (<i>p</i> = 0.001) and CAT levels from 15.22 ± 0.98 to 25.36 ± 1.12 U/mg protein (<i>p</i> = 0.002). <i>Conclusions</i>: Bosentan exerts cardioprotective effects in rats subjected to lung I/R injury by reducing myocardial damage, inflammation, and oxidative stress. These findings suggest that bosentan may serve as a potential therapeutic agent for preventing remote organ injury associated with pulmonary I/R. |
| format | Article |
| id | doaj-art-2573bdceda6542d19ca3e16d3758a49c |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-2573bdceda6542d19ca3e16d3758a49c2025-08-20T03:58:30ZengMDPI AGMedicina1010-660X1648-91442025-07-01617129810.3390/medicina61071298Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion InjuryŞevki Mustafa Demiröz0Ayşegül Küçük1Esra Tekin2Sibel Söylemez3Hanife Yılmaz4Şaban Cem Sezen5Muharrem Atlı6Hüseyin Demirtaş7Abdullah Özer8Yusuf Ünal9Mustafa Arslan10Department of Thoracic Surgery, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyDepartment of Physiology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya 43000, TurkeyDepartment of Physiology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya 43000, TurkeyApplication and Research Centre for Life Sciences, Gazi University, Ankara 06830, TurkeyDepartment of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyDepartment of Histology and Embryology, Kırıkkale University Faculty of Medicine, Kırıkkale 71450, TurkeyDepartment of Histology and Embryology, Kırıkkale University Faculty of Medicine, Kırıkkale 71450, TurkeyDepartment of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyDepartment of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyDepartment of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyApplication and Research Centre for Life Sciences, Gazi University, Ankara 06830, Turkey<i>Objective</i>: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia–reperfusion (I/R) injury, with a focus on myocardial tissue involvement. <i>Methods</i>: Twenty-four male Wistar rats were randomly assigned to four groups: sham, bosentan, I/R, and I/R + bosentan. Lung I/R injury was induced by hilar clamping for 45 min, followed by 60 min of reperfusion. Bosentan (30 mg/kg) was administered intraperitoneally 30 min prior to the procedure. Myocardial tissue was evaluated histopathologically for structural disorganization, inflammation, fibrosis, and edema. TGF-β1 protein levels in myocardial tissue were compared across the groups using β-actin as the loading control. ELISA was used to quantify ET-1, NF-κB, and p53 levels, while spectrophotometric analysis was employed to assess MDA levels and the activities of SOD and CAT enzymes in heart tissue. <i>Results</i>: The I/R group exhibited significant myocardial disorganization, inflammation, and interstitial edema compared to the sham and bosentan groups. Bosentan treatment markedly ameliorated these histopathological alterations. Additionally, the I/R group showed elevated levels of ET-1, NF-κB, p53, and MDA, along with reduced SOD and CAT activities; these changes were significantly attenuated by bosentan administration. Bosentan treatment significantly reduced myocardial ET-1 levels (from 136.88 ± 5.02 to 120.18 ± 2.67 nmol/g, <i>p</i> = 0.003), NF-κB levels (from 0.87 ± 0.04 to 0.51 ± 0.03 ng/mg, <i>p</i> = 0.002), and TGF-β1 expression (from 1.72 ± 0.10 to 0.91 ± 0.08 relative units, <i>p</i> = 0.001). Moreover, bosentan increased antioxidant enzyme activities, elevating SOD levels from 21.45 ± 1.23 to 32.67 ± 1.45 U/mg protein (<i>p</i> = 0.001) and CAT levels from 15.22 ± 0.98 to 25.36 ± 1.12 U/mg protein (<i>p</i> = 0.002). <i>Conclusions</i>: Bosentan exerts cardioprotective effects in rats subjected to lung I/R injury by reducing myocardial damage, inflammation, and oxidative stress. These findings suggest that bosentan may serve as a potential therapeutic agent for preventing remote organ injury associated with pulmonary I/R.https://www.mdpi.com/1648-9144/61/7/1298bosentanlung ischemia–reperfusioncardioprotectionoxidative stressendothelin-1myocardial injury |
| spellingShingle | Şevki Mustafa Demiröz Ayşegül Küçük Esra Tekin Sibel Söylemez Hanife Yılmaz Şaban Cem Sezen Muharrem Atlı Hüseyin Demirtaş Abdullah Özer Yusuf Ünal Mustafa Arslan Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury Medicina bosentan lung ischemia–reperfusion cardioprotection oxidative stress endothelin-1 myocardial injury |
| title | Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury |
| title_full | Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury |
| title_fullStr | Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury |
| title_full_unstemmed | Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury |
| title_short | Cardioprotective Effects of Bosentan in Rats Subjected to Lung Ischemia–Reperfusion Injury |
| title_sort | cardioprotective effects of bosentan in rats subjected to lung ischemia reperfusion injury |
| topic | bosentan lung ischemia–reperfusion cardioprotection oxidative stress endothelin-1 myocardial injury |
| url | https://www.mdpi.com/1648-9144/61/7/1298 |
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