OXIDATIVE STRESS IN COMPLEMENT-MEDIATED HEMOLYSIS: THE AMELIORATING EFFECT OF FERMENTED PAPAYA PREPARATION
(Abstract release date: 05/19/16)
EHA Library. Fibach E. 06/09/16; 133015; E1466
Disclosure(s): The study was partially supported by Osato Co. Japan
Prof. Eitan Fibach
Contributions
Contributions
Abstract
Abstract: E1466
Type: Eposter Presentation
Background
The complement (C') and the redox systems 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. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation and by correcting their cellular damage.
Aims
Using experimental model systems, we studied the interaction between the C' and the redox systems in C'-mediated hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) and in Auto-Immune Hemolytic Anemia (AIHA), and the ameliorating effect of fermented papaya preparation (FPP), an antioxidant-containing product of yeast fermentation of Carica papaya Linn.
Methods
PNH-like cells were generated by treating normal human red blood cells (RBC) with the sulphydryl compound 2-aminoethyl isothiouronium bromide. AIHA was simulated by treating group-A RBC with anti-blood group A antibodies. Both treated RBC were incubated with fresh (C'-containing) autologous or O-type serum. Reactive oxygen species (ROS), as a parameter of oxidative stress, and the surface C'-protecting CD55 and CD59 antigens were measured by flow cytometry.
Results
The sulphydryl-treated RBC demonstrated a PNH-like phenotype manifested by reduced surface expression of CD55 and CD59. In both systems, treated RBC underwent hemolysis about 40 min following interaction with activated C'. Hemolysis was preceded by an abrupt increase in ROS generation. Inactivation of the C’, either by heat (56oC for 30 min) or by the addition of an anti-C’ antibody, effectively reduced the ROS generation and hemolysis, indicating both are mediated by active C'. Addition of FPP (20 mg/ml) during the exposure to activated C' significantly reduced ROS generation and hemolysis.
Conclusion
The present results suggest that oxidative stress, in conjunction with activated C', may be involved the underlying symptoms of PNH and AIHA such as intra- and extra-vascular hemolysis. Currently, a humanized monoclonal antibody that specifically targets the C' protein C5 is the main treatment modality for PNH and some other hemolytic anemias. The present results raise the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Since FPP is well tolerated and relatively inexpensive compared to the humanized anti-C' monoclonal antibodies, its use may be considered as an alternative or an adjuvant therapeutic modality in PNH and other C'-mediated hemolytic anemias.
Session topic: E-poster
Keyword(s): Anemia, Antioxidants, Complement, Hemolysis
Type: Eposter Presentation
Background
The complement (C') and the redox systems 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. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation and by correcting their cellular damage.
Aims
Using experimental model systems, we studied the interaction between the C' and the redox systems in C'-mediated hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) and in Auto-Immune Hemolytic Anemia (AIHA), and the ameliorating effect of fermented papaya preparation (FPP), an antioxidant-containing product of yeast fermentation of Carica papaya Linn.
Methods
PNH-like cells were generated by treating normal human red blood cells (RBC) with the sulphydryl compound 2-aminoethyl isothiouronium bromide. AIHA was simulated by treating group-A RBC with anti-blood group A antibodies. Both treated RBC were incubated with fresh (C'-containing) autologous or O-type serum. Reactive oxygen species (ROS), as a parameter of oxidative stress, and the surface C'-protecting CD55 and CD59 antigens were measured by flow cytometry.
Results
The sulphydryl-treated RBC demonstrated a PNH-like phenotype manifested by reduced surface expression of CD55 and CD59. In both systems, treated RBC underwent hemolysis about 40 min following interaction with activated C'. Hemolysis was preceded by an abrupt increase in ROS generation. Inactivation of the C’, either by heat (56oC for 30 min) or by the addition of an anti-C’ antibody, effectively reduced the ROS generation and hemolysis, indicating both are mediated by active C'. Addition of FPP (20 mg/ml) during the exposure to activated C' significantly reduced ROS generation and hemolysis.
Conclusion
The present results suggest that oxidative stress, in conjunction with activated C', may be involved the underlying symptoms of PNH and AIHA such as intra- and extra-vascular hemolysis. Currently, a humanized monoclonal antibody that specifically targets the C' protein C5 is the main treatment modality for PNH and some other hemolytic anemias. The present results raise the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Since FPP is well tolerated and relatively inexpensive compared to the humanized anti-C' monoclonal antibodies, its use may be considered as an alternative or an adjuvant therapeutic modality in PNH and other C'-mediated hemolytic anemias.
Session topic: E-poster
Keyword(s): Anemia, Antioxidants, Complement, Hemolysis
Abstract: E1466
Type: Eposter Presentation
Background
The complement (C') and the redox systems 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. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation and by correcting their cellular damage.
Aims
Using experimental model systems, we studied the interaction between the C' and the redox systems in C'-mediated hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) and in Auto-Immune Hemolytic Anemia (AIHA), and the ameliorating effect of fermented papaya preparation (FPP), an antioxidant-containing product of yeast fermentation of Carica papaya Linn.
Methods
PNH-like cells were generated by treating normal human red blood cells (RBC) with the sulphydryl compound 2-aminoethyl isothiouronium bromide. AIHA was simulated by treating group-A RBC with anti-blood group A antibodies. Both treated RBC were incubated with fresh (C'-containing) autologous or O-type serum. Reactive oxygen species (ROS), as a parameter of oxidative stress, and the surface C'-protecting CD55 and CD59 antigens were measured by flow cytometry.
Results
The sulphydryl-treated RBC demonstrated a PNH-like phenotype manifested by reduced surface expression of CD55 and CD59. In both systems, treated RBC underwent hemolysis about 40 min following interaction with activated C'. Hemolysis was preceded by an abrupt increase in ROS generation. Inactivation of the C’, either by heat (56oC for 30 min) or by the addition of an anti-C’ antibody, effectively reduced the ROS generation and hemolysis, indicating both are mediated by active C'. Addition of FPP (20 mg/ml) during the exposure to activated C' significantly reduced ROS generation and hemolysis.
Conclusion
The present results suggest that oxidative stress, in conjunction with activated C', may be involved the underlying symptoms of PNH and AIHA such as intra- and extra-vascular hemolysis. Currently, a humanized monoclonal antibody that specifically targets the C' protein C5 is the main treatment modality for PNH and some other hemolytic anemias. The present results raise the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Since FPP is well tolerated and relatively inexpensive compared to the humanized anti-C' monoclonal antibodies, its use may be considered as an alternative or an adjuvant therapeutic modality in PNH and other C'-mediated hemolytic anemias.
Session topic: E-poster
Keyword(s): Anemia, Antioxidants, Complement, Hemolysis
Type: Eposter Presentation
Background
The complement (C') and the redox systems 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. Antioxidants ameliorate oxidative stress by preventing generation of free radicals, by scavenging and preventing their accumulation and by correcting their cellular damage.
Aims
Using experimental model systems, we studied the interaction between the C' and the redox systems in C'-mediated hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) and in Auto-Immune Hemolytic Anemia (AIHA), and the ameliorating effect of fermented papaya preparation (FPP), an antioxidant-containing product of yeast fermentation of Carica papaya Linn.
Methods
PNH-like cells were generated by treating normal human red blood cells (RBC) with the sulphydryl compound 2-aminoethyl isothiouronium bromide. AIHA was simulated by treating group-A RBC with anti-blood group A antibodies. Both treated RBC were incubated with fresh (C'-containing) autologous or O-type serum. Reactive oxygen species (ROS), as a parameter of oxidative stress, and the surface C'-protecting CD55 and CD59 antigens were measured by flow cytometry.
Results
The sulphydryl-treated RBC demonstrated a PNH-like phenotype manifested by reduced surface expression of CD55 and CD59. In both systems, treated RBC underwent hemolysis about 40 min following interaction with activated C'. Hemolysis was preceded by an abrupt increase in ROS generation. Inactivation of the C’, either by heat (56oC for 30 min) or by the addition of an anti-C’ antibody, effectively reduced the ROS generation and hemolysis, indicating both are mediated by active C'. Addition of FPP (20 mg/ml) during the exposure to activated C' significantly reduced ROS generation and hemolysis.
Conclusion
The present results suggest that oxidative stress, in conjunction with activated C', may be involved the underlying symptoms of PNH and AIHA such as intra- and extra-vascular hemolysis. Currently, a humanized monoclonal antibody that specifically targets the C' protein C5 is the main treatment modality for PNH and some other hemolytic anemias. The present results raise the possibility that treatment with antioxidants might be considered as a potential therapeutic modality for C'-mediated hemolytic anemias. Since FPP is well tolerated and relatively inexpensive compared to the humanized anti-C' monoclonal antibodies, its use may be considered as an alternative or an adjuvant therapeutic modality in PNH and other C'-mediated hemolytic anemias.
Session topic: E-poster
Keyword(s): Anemia, Antioxidants, Complement, Hemolysis
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