Key result
Ivabradine mitigates cisplatin-induced cardiac injury in rats by reducing oxidative stress and inflammation.
Why the study?
Ivabradine may potentially mitigate drug-induced cardiotoxicity, leading researchers to investigate its protective effect and underlying mechanisms against cisplatin-induced cardiac damage.
Does ivabradine prevent cisplatin-induced cardiotoxicity in rats?
Does ivabradine prevent cisplatin-induced cardiotoxicity in rats?
Ivabradine mitigates cisplatin-induced cardiotoxicity in rats by reducing oxidative stress and inflammation and regulating MLCP/PKG, MEK/ERK pathways, and miRNA-34a levels.
IVA may attenuate cisplatin cardiotoxicity in preclinical models; leaves open clinical translation and safety.
BACKGROUND: Ivabradine (IVA), a broad-spectrum inhibitor of HCN cation channels, is recognized for enhancing cardiac function in the treatment of cardiovascular diseases and may serve as a potential therapeutic agent for mitigating drug-induced cardiotoxicity. This study aimed to investigate the protective effect of IVA against cardiac damage induced by cisplatin (Cis) and to elucidate the underlying mechanisms. METHODS: We investigated the impact of IVA (5 mg/kg, orally for 28 consecutive days) on Cisplatin-induced cardiac injury (7.5 mg/kg intraperitoneally on day 5) in rats. Biomarkers of oxidative stress and levels of inflammatory cytokines in cardiac tissue were assessed. H&E staining was employed to identify histopathological alterations in cardiac tissue. The molecular mechanisms of IVA in ameliorating cardiac injury were examined. RESULTS: The results indicated that IVA enhanced cardiac tissue structure by suppressing the pathological alterations observed in H&E staining. IVA demonstrated antioxidant and anti-inflammatory properties through reducing malonaldehyde (MDA), NADPH oxidase, tumor necrosis factor-α (TNF-α), and interleukins (IL-1β and IL-6) levels, while elevating superoxide dismutase (SOD), IL-10, and eNOS levels. IVA diminished the expression of cAMP response element-binding protein (CREB), Extracellular signal-regulated kinase (ERK), Mitogen-activated protein kinase kinase (MEK), Protein Kinase C-epsilon (PKC epsilon), and microRNA-34a (miRNA-34a), while enhancing the expression of Protein Kinase G (PKG), Myosin Light Chain Phosphatase (MLCP), and Rapidly Accelerated Fibrosarcoma (Raf-1), as confirmed by western blotting and PCR results. Furthermore, its impact on cardiac tissue viability was supported by increased B-cell lymphoma 2 (Bcl2) levels and decreased caspase-3 staining in immunohistopathology. CONCLUSION: IVA may significantly mitigate cardiac injury in Cis-induced cardiotoxicity through regulating multiple pathways and miRNA-34a levels.
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Aldabaan et al. (2026) studied Cisplatin-induced cardiotoxicity. Ivabradine vs. Cisplatin alone was evaluated on Cardiac tissue structure, oxidative stress, inflammatory cytokines, and molecular pathways. Ivabradine mitigated cisplatin-induced cardiac injury in rats by reducing oxidative stress and inflammation, and regulating MLCP/PKG, MEK/ERK pathways, and miRNA-34a levels.
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