Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity

Objective(s): Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity. Materials and Methods: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured. Results: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly  (P 0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB.Conclusion: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.