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.