Oxidative stress in paroxysmal nocturnal hemoglobinuria and other conditions of complement-mediated hemolysis

The complement (C') system and redox status play important roles in the physiological functioning of the body, such as the defense system, but they are also involved in various pathological conditions, including hemolytic anemia. Herein, we review the interaction between the C' and the redox systems in C'-mediated hemolytic anemias, paroxysmal nocturnal hemoglobinuria (PNH) and autoimmune hemolytic anemia, including acute hemolytic transfusion reaction. Blood cells in these diseases have been shown to have increased oxidative status, which was further elevated by interaction with activated C'. The results suggest that oxidative stress, in conjunction with activated C', may cause the underlying symptoms of these diseases, such as intra- and extravascular hemolysis and thrombotic complications. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation, and by correcting their cellular damage. Antioxidants have been shown to reduce the oxidative stress and inhibit hemolysis as well as platelet activation mediated by activated C'. This raises the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Currently, eculizumab, a humanized monoclonal antibody that specifically targets the C' protein C5, is the main treatment modality for PNH. However, because antioxidants are well tolerated and relatively inexpensive, they might be considered as potential adjuvants or an alternative therapeutic modality for PNH and other C'-mediated hemolytic anemias.