EFFECT OF METFORMIN AND ROSUVASTATIN ON ERYTHROCYTES OF PATIENTS WITH SICKLE CELL DISEASE: AN IN-VITRO STUDYAbstract
Objectives: Sickle cell disease (SCD) is a common hereditary blood disease with a progressive clinical course and multiple end organs damage. Due to its intercalated pathophysiology, several trials have been conducted targeting its pathophysiology in an attempt to modify the clinical course and minimize complications. Metformin and rosuvastatin are known to have pleiotropic effects such as antioxidant, anti-inflammatory and vasculoprotective properties making them a candidate for testing in SCD. Aim: To test possible effects of metformin and rosuvastatin on oxidative stress, erythrocytes deformability, %hemolysis in blood samples of patients with SCD. Materials and Methods: Blood samples were obtained from 36 SCD patients at stable conditions. The samples were incubated with metformin (1 mg/ml) or rosuvastatin (0.25 mg/ml). Oxidative stress was induced by incubating the samples with H2O2 for 30 min. Reduced glutathione (GSH), lipid peroxidation products (thiobarbituric acid reactive species TBARS), % hemolysis was determined by spectrophotometer and erythrocytes deformability by filtration method. Result: Treatment of blood with metformin or rosuvastatin resulted in a significant reduction in TBARS level (-32%, -37% for metformin and rosuvastatin respectively) with an increase in GSH level (+ 68%, + 75% respectively). Metformin and rosuvastatin reduced % hemolysis, P=0.01. Metformin treatment but not rosuvastatin significantly improved erythrocytes deformability, P=0.01. Conclusion: It is concluded that metformin and rosuvastatin, favorably changed TBARS and GSH levels in blood samples of SCD in which oxidative stress was induced by H2O2. These changes possibly resulted in reduced % hemolysis and improved erythrocytes deformability.