Bosentan Reduces Myocardial Ischemia-Reperfusion Injury in Rats

Abstract

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.