Modulatory Role of Melatonin in Cyclophosphamide‐Treated Platelets: Insights From Ex Vivo Oxidative Stress Model

Cyclophosphamide (CYP) is implicated in oxidative stress (OS)-related platelet destruction during chemotherapy, leading to thrombocytopenia. Antioxidants can potentially attenuate the side effects of drugs and improve therapeutic outcomes. Melatonin is highly permeable and has radical scavenging and antioxidant enzyme-stimulating activity. This study investigates the influence of melatonin on platelets during CYP-induced OS under ex vivo conditions. Platelets isolated from the whole blood of male Wistar rats (n = 5) were categorized and treated as follows: Controls (CON) and Experimentals: (i) CYP, (ii) melatonin (MEL), and (iii) CYP+melatonin (CYP + MEL). Antioxidant defenses, OS and platelet function markers were assessed. Catalase, total antioxidant capacity (TAC), and lactate dehydrogenase decreased; ATP secretion, activation and cell viability decreased; and glucose and aggregation increased in CYP compared to CON. Catalase, TAC and glucose were maintained in MEL compared to CON. However, catalase increased, thereby decreasing lipid peroxidation and enhancing activation and aggregation in CYP + MEL compared to CYP. Melatonin mitigates CYP-induced cellular damage by scavenging ROS and augmenting antioxidant defenses. Platelets possess a complex network of signaling cascades, and can serve as ex vivo models to study platelet dysfunction. They can provide insights into platelet behavior under simulated physiological and pathological conditions.