Cardioprotective action of apocynin in isoproterenol-induced cardiac damage is mediated through Nrf-2/HO-1 signaling pathway.

This investigation evaluated the therapeutic benefit of apocynin in isoproterenol (ISO)-induced cardiac damage in rats. ISO-administered male Wistar rats were treated with apocynin for 2 weeks. Blood plasma and left ventricle of heart tissues were collected and analyzed for oxidative stress-related parameters such as malondialdehyde (MDA), advanced oxidation protein product (AOPP), and nitric oxide (NO). The activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase were also measured. The gene expressions of oxidative stress-related proteins such as Nrf-2, HO-1, and HO-2 in cardiac tissues were also measured. In silico studies like molecular docking and molecular dynamics were also performed to detect how apocynin interacts with NADPH and nitric oxide synthase at the molecular level. This investigation revealed significant elevation of serum transferase enzymes and creatinine kinase-Muscle Brain (CK-MB) activities in ISO-administered rats compared to the control. Apocynin effectively normalized the serum transferases and CK-MB activities in the blood of ISO-stressed rats. Moreover, ISO-induced elevations of MDA, NO, and AOPP levels were also suppressed by apocynin treatment. Consistently, apocynin restored the reduced SOD and catalase activities in ISO-administered rats. This restoration of enzyme activity might be due to the increased expression of Nrf-2 and HO-1 and reduced expression of iNOS and TNF-α in ISO-administered rats. Histological analysis revealed that apocynin treatment ameliorated the mononuclear cell adherence and fibrosis in the cardiac tissue of ISO-administered rats. Computational studies also support the experimental findings. This study demonstrates that apocynin prevents ISO-induced cardiac injury not only by preventing inflammation but also by empowering the antioxidant defense system.