Candesartan significantly attenuated cisplatin-induced biochemical and histological myocardial injury, restored redox homeostasis, and suppressed TLR-4/NF-κB/IRF-3/AP-1 signaling in rats.
Does candesartan mitigate cisplatin-induced myocardial injury in male Wistar rats?
Candesartan shows promise as a cardioprotective adjunct against cisplatin-induced cardiotoxicity in a rat model by mitigating oxidative stress and inflammation.
Cisplatin (CIS) is effective chemotherapeutic agent, but its clinical use is limited by adverse effects, including cardiotoxicity. Safe cardioprotective agents that can be rapidly translated into oncology practice remain an unmet need. This study evaluated whether candesartan (CAN), a clinically approved angiotensin II receptor blocker (ARB), protects against CIS-induced myocardial injury. Male Wistar rats were randomized into control, CAN, CIS, and CAN+CIS groups. CAN (5 mg/kg, oral) was administered for 10 days and CIS (7 mg/kg, i.p.) was injected on day 7. Serum cardiac biomarkers were assessed, oxidative and inflammatory mediators were quantified in cardiac tissue, and histopathology and immunohistochemistry were performed. CIS caused marked myocardial injury, evidenced by elevated cTnI, CK-MB, AST, and LDH, structural degeneration, and necrosis. Oxidative stress was pronounced, with increased lipid peroxidation and MPO activity and depleted antioxidant defenses, accompanied by downregulation of cytoglobin. CAN significantly attenuated biochemical and histological injury, restored redox homeostasis, and preserved cytoglobin expression. CIS also upregulated TLR-4, NF-κB, IRF-3, c-Fos, c-Jun, iNOS, and pro-inflammatory cytokines, whereas CAN markedly suppressed these changes. Molecular docking analysis showed the binding of CAN with cytoglobin, NF-κB p65, IRF-3, and c-Fos/c-Jun complex. In conclusion, CAN confers protection against CIS-induced myocardial damage by mitigating oxidative stress, enhancing antioxidants, and suppressing TLR-4/NF-κB/IRF-3/AP-1 signaling. These findings highlight CAN as a promising adjunct to alleviate CIS-induced cardiotoxicity and preserve cardiovascular health in cancer patients undergoing CIS chemotherapy. However, further investigations and clinical trials are needed to validate these preclinical data.
Hassanein et al. (2026) studied Cisplatin-induced myocardial injury. Candesartan vs. Control, Cisplatin alone was evaluated on Myocardial injury (cTnI, CK-MB, AST, LDH, structural degeneration, necrosis, oxidative stress, inflammatory mediators). Candesartan significantly attenuated cisplatin-induced biochemical and histological myocardial injury, restored redox homeostasis, and suppressed TLR-4/NF-κB/IRF-3/AP-1 signaling in rats.