Limonene as a potential cardioprotective agent: mechanistic intuitions into antioxidant and anti-apoptotic properties in isoproterenol-induced ischemia in rats

Background and aims: Excessive oxidative stress and increased apoptosis are the main culprits to heart damage associated with ischemic heart disease. This study aimed to demonstrate the cardioprotective properties of limonene (LIM), a monoterpenoid compound, in isoproterenol-induced ischemia (ISO-I) in rats. Methods: Forty male Wistar rats were divided into five groups (n=8). Normal saline (1 mL/kg) and LIM at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg were administered for seven days before the induction of ischemia by ISO. Creatine kinase-MB (CK-MB), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capability (TAC), and relative expression of BCL2 and BAX genes underwent measurement. Results: CK-MB (3.73±0.560 versus 0.888±0.317), CPK (901±72.2 versus 397±33.5), LDH (1992±176 versus 821±94.1), and MDA levels in the serum (65.6±11.0 versus 28.3±4.75) and heart (104±8.70 versus 65.3±7.46) samples significantly increased following ischemia in the treatment groups compared to the control group (P<0.001 for all markers). Ischemia decreased TAC in the heart (324±45.0 versus 588±64.5) and serum (202±23.0 versus 388±45.9) samples compared to the control counterparts (P<0.001 for both samples). ISO-I is associated with a decrease in Bcl-2 (0.880±0.118 versus 1.74±0.178) and an increase in BAX (2.75±0.124 versus 1.08±0.0938) gene expression in comparison to the control group (P<0.001 for both genes). LIM could reverse the aforementioned heart damage-related biomarkers in the serum and heart samples. Finally, LIM improved histopathological disarrangement following ischemia. Conclusion: The findings revealed that LIM, at least partially due to its antioxidant and anti-apoptotic potentials, exerted cardioprotection against ISO-induced heart ischemia in rats.