Cardiovascular research institute, Isfahan University of Medical Sciences ARYA Atherosclerosis Journal 1735-3955 22 Issue 4 2026 07 01 Protective effects of vanillic acid against isoprenaline‑induced heart failure in Wistar rats: A biochemical and histological investigation 33346 10.48305/arya.2026.45520.3085 EN Mojtaba Khaksarian Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Naser Pajouhi Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Afshin Nazari Nazari Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran 0000-0002-1863-1092 Raheleh Assaei Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Faraz Souri Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran 0009-0008-3228-8527 Journal Article 2025 08 11 <strong>BACKGROUND:</strong> Heart failure (HF) continues to pose a major health concern worldwide, frequently arising from ongoing myocardial damage driven by oxidative stress, inflammatory processes, and programmed cell death. While synthetic medications are widely used, natural compounds with multi-targeted actions are gaining attention. Vanillic acid (VA), a plant-derived phenolic compound, is suggested to possess cardioprotective properties; yet, its effects in experimental HF models remain underexplored.<br><strong>METHODS:</strong> This study evaluated the impact of VA pretreatment on isoprenaline (ISO)-induced HF in male Wistar rats. A total of forty animals were randomly allocated into four distinct groups: sham, VA, ISO, and ISO + VA. ISO was administered subcutaneously to induce cardiac injury, while VA was given orally for 10 days prior to ISO exposure. Biochemical markers of myocardial damage, oxidative stress, inflammatory cytokines, infarct size, and apoptotic gene expression (Bax, Bcl-2) were assessed through ELISA, histological staining, and real-time PCR.<br><strong>RESULTS:</strong> ISO administration caused significant elevation in cardiac enzymes (LDH, CK-MB, cTn-I), pro-inflammatory markers (IL-1β, TNF-α), lipid peroxidation (MDA), and Bax expression, along with reduced antioxidant enzyme activity (CAT, SOD, GPx), IL-10, and Bcl-2 levels. VA pretreatment mitigated these alterations, demonstrating a notable decrease in infarct size, oxidative damage, inflammation, and apoptosis. No adverse effects were observed in the VA-only group.<br><strong>CONCLUSION:</strong> VA exhibited substantial cardioprotective effects against ISO-induced myocardial injury, likely through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. The results indicate that VA could be a valuable natural adjunct in the management of HF.