Resveratrol and tetrahydroisoquinoline effects on neutrophil sensitivity to NETosis formation in low-risk essential thrombocythemia patients

Introduction: Recent studies scrutinize how NETosis (a unique cell death mechanism of neutrophil), impacts thrombosis patients with essential thrombocythemia (ET). This research evaluates the susceptibility of ET neutrophils to form NETs and tests two potential inhibitors, resveratrol (RSV) and tetrahydroisoquinoline (THIQ), in vitro. Methods: Platelet-rich plasma from low-risk ET patients was used, along with neutrophils from both patients and controls. NET formation assays, with or without RSV and THIQ treatment after LPS stimulation, were conducted in a CO2 incubator. Evaluation included flow cytometry and fluorescence microscopy for NET formation and ELISA for TNF alpha, IL8, and vWF:Ag levels in patient and control plasma. Results: Neutrophils from ET patients released more NETs than controls, confirmed by flow cytometry and fluorescence microscopy. Additionally, patients had significantly higher plasma levels of IL8 and TNF alpha compared to controls, while RSV was more effective than THIQ in reducing NETosis rates in these patients. Conclusions: In ET patients, a platelet counts over 1 million indicates the need for preventive treatment against thrombotic events. Similarly, in this study, RSV and THIQ significantly reduced the rate of NETosis in ET patients with higher platelet counts, and this role was more prominent in the case of the second inhibitor (RSV).