Modulation of thrombin-induced human platelet activation and oxidative stress by polyamines

The effects of three polyamines, spermine, spermidine, and putrescine, on thrombin-induced platelet activation and function were investigated. Our findings demonstrate that polyamines significantly influence platelet activity, with spermine exhibiting the most pronounced effects. Polyamines dose-dependently were able to inhibit platelet aggregation and CD62P exposure induced by thrombin, as well as the rise in intracellular calcium concentration, indicating the involvement of polyamines in platelet activation signaling pathways. Beyond their effects on platelet function, polyamines show potent antioxidant activity. In thrombin-stimulated platelets, polyamines, and spermine in particular, inhibit reactive oxygen species and superoxide anion production, as well as the consequent lipid peroxidation, demonstrating a protective effect against oxidative stress. Furthermore, polyamines restored mitochondrial function by improving oxidative phosphorylation efficiency. Polyamines can restore the oxygen consumption rate and ATP production, indicating a role in maintaining cellular energy homeostasis under pro-thrombotic conditions. These findings suggest that polyamines, particularly spermine, could have an interesting therapeutic role since they can modulate platelet activation, oxidative stress, and oxidative phosphorylation efficiency. The restoration of platelet function through treatment with polyamines could have a protective effect against a pro-thrombotic state, which is involved in venous and arterial thrombosis, which contributes to cardiovascular diseases.