ZEYNEP YIĞMAN, HÜSEYİN DEMİRTAŞ, MEHMET BURAK GÜLCAN, ABDULLAH ÖZER, ALİ DOĞAN DURSUN, AYŞEGÜL KÜÇÜK, MUSTAFA ARSLAN
Journal of Updates in Cardiovascular Medicine - 2025;13(3):135-145
Objectives This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, against myocardial ischemia-reperfusion injury (MIRI) in rats. Materials and Methods Twenty-four adult Wistar-Albino rats were randomly divided into four groups: control, bosentan only, myocardial ischemia-reperfusion (MIR), and MIR-bosentan (MIR-B). Ischemia was induced by ligation of the left anterior descending coronary artery for 30 minutes, followed by 90 minutes of reperfusion. Bosentan was administered intraperitoneally at 30 mg/kg during ischemia in the MIR-B group. Histopathological evaluation assessed neutrophil infiltration, cardiomyocyte damage, tissue edema, and hemorrhage, while biochemical analyses measured total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and paraoxonase-1 (PON-1) activity in myocardial tissue. RESULTS The MIR group showed significantly increased histopathological injury scores, including neutrophil infiltration, cardiomyocyte damage, edema, and hemorrhage, compared to control and bosentan-only groups (p<0.001). Bosentan treatment significantly reduced these injury scores in the MIR-B group compared to the MIR group (p<0.05). Biochemically, the MIR group exhibited elevated TOS and OSI levels and reduced TAS and PON-1 activity, indicating oxidative stress. Bosentan administration significantly improved these parameters by lowering TOS and OSI levels, and by increasing TAS and PON-1 activity compared to the MIR group (p<0.05). CONCLUSION In conclusion, bosentan demonstrated significant protective effects against MIRI by attenuating histological damage and oxidative stress in rat myocardium. These findings suggest that endothelin receptor antagonism with bosentan may offer a promising therapeutic approach to reduce myocardial injury following ischemia-reperfusion events such as those occurring during coronary artery bypass grafting. Further studies are needed to explore its clinical potential.
