Complement-mediated hemolysis: The involvement of oxidative stress and the ameliorating effect of Fermented Papaya Preparation

Objectives We studied the involvement of serum-complement (C') and oxidative stress in the hemolytic anemias Paroxysmal Nocturnal Hemoglobinuria (PNH) and Auto-Immune Hemolytic Anemia (AIHA), and the effect of Fermented Papaya Preparation (FPP), an antioxidant-containing yeast fermentation product of Carica papaya Linn. Methodology Normal human red blood cells (RBC) treated with the sulphydryl compound 2-aminoethyl isothiouronium bromide demonstrated a PNH-phenotype (reduced surface expression of the protecting CD55 and CD59 antigens). AIHA was simulated by treating group-A RBC with anti-A antibodies. Both samples were exposed to C'-containing, Otype, serum. Results Hemolysis, which was developed 40 min later, was preceded by an abrupt increase in reactive oxygen species (ROS). Both ROS and hemolysis were reduced by inactivating the C’ (by heat or by an anti-C’ antibody), and by FPP (20 mg/ml), indicating the involvement of C' and oxidative stress, respectively. One PNH patient treated with FPP showed reduced hemolysis. Conclusion Currently, a humanized anti-C' monoclonal antibody is the main treatment for PNH and some other hemolytic anemias. Our results suggest a therapeutic role for antioxidants. Since FPP is well tolerated and relatively inexpensive, its use may be considered as an alternative or adjuvant therapy for PNH and other C'-mediated hemolytic anemias. List of abbreviations: Complement (C'), Paroxysmal Nocturnal Hemoglobinuria (PNH), phosphatidylinositol glycan complementation class A (PIG-A), Auto-Immune Hemolytic Anemia (AIHA), Fermented Papaya Preparation (FPP), red blood cells (RBC), reactive oxygen species (ROS), glycosylphosphatidylinositol (GPI), mean fluorescence channel (MFC), Phosphatidylserine (PS).