title: Oxidative stress in sickle cell disease: an overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies.
abstract: Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O2(-)) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body. Sickle hemoglobin molecules suffer repeated polymerization/depolymerization generating greater amounts of reactive oxygen species, which can lead to a cyclic cascade characterized by blood cell adhesion, hemolysis, vaso-occlusion, and ischemia-reperfusion injury. In other words, sickle cell disease is intimately linked to a pathophysiologic condition of multiple sources of pro-oxidant processes with consequent chronic and systemic oxidative stress. For this reason, newer therapeutic agents that can target oxidative stress may constitute a valuable means for preventing or delaying the development of organ complications.
authors.affiliation: Hemoglobin and Hematologic Genetic Diseases Laboratory, Department of Biology, Sao Paulo State University "Julio de Mesquita Filho," 15054-000 Sao Jose do Rio Preto, SP, Brazil; Laboratory of Aquatic Contamination Biomarkers, Department of Chemistry and Environmental Sciences, Sao Paulo State University "Julio de Mesquita Filho," 15054-000 Sao Jose do Rio Preto, SP, Brazil.
authors.forename: Danilo Grunig Humberto
authors.initials: DGH
authors.lastname: Silva
authors.affiliation: Hemoglobin and Hematologic Genetic Diseases Laboratory, Department of Biology, Sao Paulo State University "Julio de Mesquita Filho," 15054-000 Sao Jose do Rio Preto, SP, Brazil.
authors.forename: Edis
authors.initials: E
authors.lastname: Belini Junior
authors.affiliation: Laboratory of Aquatic Contamination Biomarkers, Department of Chemistry and Environmental Sciences, Sao Paulo State University "Julio de Mesquita Filho," 15054-000 Sao Jose do Rio Preto, SP, Brazil.
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: de Almeida
authors.affiliation: Hemoglobin and Hematologic Genetic Diseases Laboratory, Department of Biology, Sao Paulo State University "Julio de Mesquita Filho," 15054-000 Sao Jose do Rio Preto, SP, Brazil. Electronic address: claudiabonini@sjrp.unesp.br.
authors.forename: Claudia Regina
authors.initials: CR
authors.lastname: Bonini-Domingos
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000503:physiopathology*; D000975:Antioxidants / Q000627:therapeutic use*; D002448:Cell Adhesion; D004912:Erythrocytes / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000097:blood; D015427:Reperfusion Injury / Q000150:complications; D055544:beta-Globins / Q000235:genetics
chemical_list: D000975:Antioxidants; D006451:Hemoglobin, Sickle; D017382:Reactive Oxygen Species; D055544:beta-Globins
keywords: Erythrocytes; Free radicals; Hemoglobin S; Redox process