Foxo3 gene expression and oxidative status in beta-thalassemia minor subjects

Abstract

BackgroundOxidative stress may aggravate symptoms of hemolytic anemias such as beta-thalassemia. FoxO3 activation results in resistance to oxidative stress in fibroblasts and neuronal cell cultures.ObjectiveThe purpose of this research was to study FoxO3 gene expression and oxidative status in beta-thalassemia minor individuals.MethodsSixty-three subjects (42 apparently healthy individuals and 21 with beta-thalassemia minor) were analyzed at the Universidad Nacional de Tucumán, Argentina, between September 2013 and June 2014. A complete blood count, hemoglobin electrophoresis in alkaline pH and hemoglobin A2 levels were quantified. Moreover, thiobarbituric acid reactive species, erythrocyte catalase activity and iron status were evaluated. Beta-thalassemia mutations were determined by real-time polymerase chain reaction. FoxO3 gene expression was investigated by real-time reverse transcription-polymerase chain reaction using mononuclear cells from peripheral blood.ResultsSubjects were grouped as children (≤12 years), and adult women and men. The analysis of erythrocyte catalase activity/hemoglobin ratio revealed a significant difference (p-value <0.05) between healthy and beta-thalassemia minor adults, but no significant difference was observed in the thiobarbituric acid reactive species levels and FoxO3 gene expression (p-value >0.05). Thiobarbituric acid reactive species and the erythrocyte catalase activity/hemoglobin ratio were not significantly different on comparing the type of beta-thalassemia mutation (β0 or β+) present in carriers.ConclusionsThe lack of systemic oxidative imbalance demonstrated by thiobarbituric acid reactive species is correlated to the observation of normal FoxO3 gene expression in mononuclear cells of peripheral blood. However, an imbalanced antioxidant state was shown by the erythrocyte catalase activity/hemoglobin ratio in beta-thalassemia minor carriers. It would be necessary to study FoxO3 gene expression in reticulocytes to elucidate the role of FoxO3 in this pathology.

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.

“…Se refiere a aquellos individuos portadores heterocigotos del gen de esta afección [17]. Clínicamente tiene un curso más leve que aquellos con β-talasemia TDT, presentándose con una anemia más o menos marcada que no requiere tratamiento con transfusiones de sangre regulares [25]. Estos pacientes son usualmente asintomáticos [25].…”

“…Clínicamente tiene un curso más leve que aquellos con β-talasemia TDT, presentándose con una anemia más o menos marcada que no requiere tratamiento con transfusiones de sangre regulares [25]. Estos pacientes son usualmente asintomáticos [25]. A menudo tienen anemia leve que varía entre 9 y 11 g/dl; que se caracteriza por ser microcítica hipocrómica y en ocasiones, incluso pueden tener niveles normales de hemoglobina [26].…”

Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran

“…Thalassemia is a common genetic disease associated with global health problems. 1 Compared with other regions, Iran is one of the countries with a higher prevalence of thalassemia. 2 Beta-thalassemia is caused by mutations in the beta-globin gene on chromosome 11, resulting in decreased or non-synthesized beta chains, leading to severe anemia.…”

Measurement the Levels of Catalase Activity, Malondialdehyde and Ferritin in Beta-thalassemia Major Patient

“…The use of iron chelation agents with antioxidants material can be useful in regulating antioxidant status in patients with beta-thalassemia major (2) Perform frequent blood transfusions in patients with beta-thalassemia major, iron levels are increased, making the red blood cells vulnerable to oxidative stress (3) Due to increased generation of free radicals and lipid peroxidation, and a decrease in total antioxidant capacity, lead to an imbalance between oxidants and antioxidants that results in oxidative stress (4) Patients with beta-thalassemia major receive regular blood transfusions monthly to prevent severe anemia and allow the normal growth and development of the body (5). Each unit of donor blood contains 420ml of blood and about 200mg of iron (6) While blood transfusions prevent many complications of severe anemia, the body is unable to get rid of the iron overload that accompanies every blood transfusion, so it is deposited in the tissues and organs, leading to damage and failure of the body's systems (7). By stimulating the formation of reactive oxygen species (ROS) causing chronic oxidative stress the excess quantities of iron convert oxidants into high-energy radicals represented by hydroxyl radicals from ROS through the Fenton/Haber-Weiss reaction (8) .…”