Casuarinin modulates renin-angiotensin-aldosterone system to counter ephedrine-induced myocardial damage in rats.

Ephedrine (EPH) is a sympathomimetic drug that showed adverse effects on different body organs such as heart. Casuarinin (CAS) is a polyphenolic agent that exhibits various biological as well as pharmacological properties. The current research was performed to explore the mitigative attributes of CAS against EPH instigated sub-chronic cardiotoxicity. Thirty-six Sprague Dawley male rats were divided into control, EPH (20 mgkg), CAS (25 mgkg) + EPH (20 mgkg), and CAS (20 mgkg) alone administered group. Our findings revealed that EPH exposure provoked the gene expression of renin (REN), angiotensinogen (AGT), angiotensin I (Ang I), angiotensin II (Ang II), angiotensin II receptor type 1 (AGTR1), aldosterone synthase (CYP11B2), and mineralocorticoid receptor (NR3C2). The enzymatic activities of heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx) (54.30 %), superoxide dismutase (SOD) (62.38 %), glutathione reductase (GSR) (54.80 %), catalase (CAT) (67.54 %), glutathione (GSH) (62.14 %) and glutathione S-transferase (GST) (44.25 %) were suppressed while the concentrations of reactive oxygen species (ROS) (2518.52 %) and malondialdehyde (MDA) (2654.55 %) were provoked after EPH intoxication. Besides, the EPH exposure exacerbated the concentration of N-terminal pro-B-type natriuretic peptide (ProBNP) (179.39), creatine kinase-myocardial band (CK-MB) (133.55 %), creatine phosphokinase (CPK) (180.72 %), C-reactive protein (CRP) (348.34 %), troponin-T (TnT) (1210.91 %), lactate dehydrogenase (LDH) (518.47 %), troponin-I (TnI) (1266.67 %) and brain natriuretic peptide (BNP) (243.34 %). The expression of Bax, and Caspase-3 were augmented while the expression of Bcl-2 was diminished after EPH administration. Moreover, EPH escalates the levels of interleukin-1beta (IL-1β) (471.71 %), cyclooxygenase-2 (COX-2) (304.16 %), tumor necrosis factor-alpha (TNF-α) (219.96 %), interleukin-6 (IL-6) (316.76 %), and nuclear factor-kappa B (NF-κB) (343.59 %) as well as significantly (p < 0.05) dysregulated the normal histology of cardiac tissues. Nevertheless, CAS treatment notably alleviated EPH instigated sub-chronic cardiac damage through the regulation of RAAS, oxidative stress, apoptosis, and inflammation. These findings suggest that CAS could be employed as cardioprotective agent against EPH intoxication.