Abstract
Background: Myocardial infarction (MI) is a leading cause of death worldwide, primarily associated with oxidative stress, inflammation, apoptosis, and ionic imbalance. Isoproterenol (ISO)-induced MI in rats mimics human cardiac injury. Flavonoids have gained attention for their antioxidant and cardioprotective effects. Isorhamnetin, a natural flavonoid, possesses potent antioxidant and anti-inflammatory properties, but its cardioprotective mechanisms in MI remain unclear. This study aimed to evaluate the protective role of isorhamnetin against ISO-induced MI in rats. Methods: Male Wistar albino rats were divided into four groups: normal control, isorhamnetin alone (10 mg/kg), ISO-induced MI (100 mg/kg, s.c., 2 days), and ISO + isorhamnetin-treated. Cardiac injury biomarkers (CK-MB, cTn-T, cTn-I), lipid peroxidation, antioxidant status (enzymatic and non-enzymatic), membrane-bound ATPase activities, and electrolyte levels were assessed. Apoptosis-related proteins were measured by ELISA and gene expression by RT-PCR. Histopathology was performed using H&E and Masson’s trichrome staining. In vitro antioxidant activity was assessed via DPPH and ABTS+ assays. Results: ISO administration significantly increased cardiac biomarkers, lipid peroxidation, apoptotic markers, electrolyte imbalance, and histological damage, while reducing antioxidant defenses and Na⁺/K⁺-ATPase activity (P<0.05). Isorhamnetin treatment mitigated these changes by restoring antioxidant enzymes, reducing oxidative stress, normalizing ATPase function and ionic balance, and inhibiting Fas-receptor and caspase-mediated apoptosis (P<0.05). Histology revealed reduced necrosis, inflammation, edema, and fibrosis. In vitro assays confirmed strong free radical scavenging activity of isorhamnetin. Conclusion: Isorhamnetin protects against ISO-induced MI by reducing oxidative stress, preserving membrane integrity, maintaining ionic homeostasis, and suppressing apoptosis. These findings highlight isorhamnetin as a promising natural cardioprotective agent for MI.