Decreased hemolysis following administration of antioxidant—fermented papaya preparation (FPP) to a patient with PNH

Abstract

Dear Editor, Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease (HSC), characterized by intravascular hemolysis [1] due to inactivating mutation of the X-linked PIG-A gene in an HSC; the gene product is essential for the synthesis of glycosylphosphatidylinositol (GPI) anchor molecules [2]. Intravascular hemolysis is a major cause of anemia in PNH. Two surface proteins, CD55 and CD59, which regulate complement activation on the cell surface are GPI-linked [3], and their deficiency explains the hypersusceptibility of PNH red blood cells (RBC) to complementmediated lysis, intravascular hemolysis, and release of free hemoglobin (Hb). Hb has a vasculotoxic potential, directly impairing endothelial function and generating inflammatory and oxidative stress [4]. Cell-free Hb disintegrates into heme and globin, and the iron from heme catalyzes the formation of reactive oxygen species (ROS) [5] causing damage to various components of the cell. Flow cytometry analyses of RBC, platelets, and polymorphonuclear cells from patients with PNH disclosed a significant increase in ROS, while reduced glutathione was decreased. Oxidative stress was more profound in cells derived from the pathological clone with a CD55–CD59 phenotype. Increased membrane lipid peroxidation was also documented in PNH RBC [6]. Consequently, there is evidence for increased oxidative stress in PNH, which might play a significant role in the pathophysiology of the disease. Indeed, in vitro treatment of PNH-RBC with antioxidants decreased their hemolysis [6]. Therefore, there is a rationale for treatment with antioxidants in order to reduce the oxidative stress and improve its clinical manifestations in PNH patients. One antioxidant is fermented papaya preparation (FPP), a natural health food product obtained by yeast biofermentation of carica papaya [7], which decreases oxidative stress both in vitro and in vivo [8].