Effects of Ivabradine (If channel inhibitor) and N-Acetylcysteine against isoprenaline-induced myocardial injury: Role of Nrf2/HO-1 signaling and inflammation suppression.

Myocardial injury, induced experimentally using Isoprenaline (ISP), involves severe oxidative stress, inflammation, and cellular damage. The present study compared the cardioprotective effects of Ivabradine (IVB), an If channel antagonist, and N-Acetylcysteine (NAC), a glutathione precursor, against ISP-induced myocardial injury. Rats were divided into 5 groups (n = 8): Control (saline), ISP (150 mg/kg i.p. for 2 days), NAC (100 mg/kg/day oral for 14 days + ISP), IVB (5 mg/kg/day oral for 14 days + ISP), and NAC + IVB. Myocardial injury was assessed by measuring serum creatine kinase-myocardial band (CK-MB), cardiac troponin I (CTnI), and cardiac tissue levels of malondialdehyde (MDA) and Glutathione (GSH). qRT-PCR was performed for the expression of Interleukin-6 (IL-6), Nuclear factor erythroid-2 related factor 2 (Nrf2), and Haemoxygenase-1 (HO-1). Histopathological analysis and immunohistochemistry for Caspase-3 (apoptosis) and VEGF were performed. The ISP group showed markedly elevated CK-MB and CTnI, significant oxidative stress (highest MDA, lowest GSH), IL-6 upregulation, suppressed antioxidant defense (Nrf2/HO-1 downregulation), and extensive tissue damage (fibrosis, elevated Caspase-3). While single treatments offered significant protection, the co-administration of NAC and IVB demonstrated superior, synergistic efficacy. In conclusion, the combined therapy of NAC and IVB offers cardioprotection by maximally boosting the antioxidant defense system, suppressing inflammation, apoptosis, and fibrosis.