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

ABSTRACT Background: Oxidative 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. Objective: The purpose of this research was to study FoxO3 gene expression and oxidative status in beta-thalassemia minor individuals. Methods: Sixty-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. Results: Subjects 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. Conclusions: The 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.

TBARS level in socioeconomical poor rural sickle cell patients of Bilaspur Zone of Chhattisgarh State.

Sickle cell disease (SCD) is an inherited disorder of hemoglobin synthesis and the oxidative stress has major role in the pathogenesis of SCD. Thiobarbituric acid reactive substances formation by lipid peroxidation is a marker of oxidative damage in membrane.The study was under taken to measure the oxidative stress in sickle cell patients of Chhattisgarh rural population because of low natural antioxidants in their diet. The patients of sickle cell anemia group (homozygous, n=9) and sickle cell trait (heterozygous, n=21) shows TBARS level 2.28±0.66μM/l and 2.23±0.7μM/l respectively as compared to control (without S.C.D) 1.25±0.41μM/l. the study shows TBARS concentration is approximately double in sickle cell disease than control.

Plasma cytokine response, lipid peroxidation and NF-kB activation in skeletal muscle following maximum progressive swimming

Our objective was to determine lipid peroxidation and nuclear factor-κB (NF-κB) activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15) adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1), 3 h after exercise (EX2) and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2 percent of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS) generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS) levels (4062.67 ± 1487.10 vs 19,072.48 ± 8738.16 nmol malondialdehyde (MDA)/mg protein, control vs EX1). Exercise also promoted NF-κB activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6) levels 3 h post-exercise (P < 0.05). Interleukin-10 (IL-10) levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05). Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-12 (IL-12), were not altered by exercise. The present findings showed that maximum swimming, as well as other exercise models, led to lipid peroxidation and NF-κB activation in skeletal muscle and increased plasma IL-6 levels. The plasma cytokine response was also marked by reduced IL-10 levels. These results were attributed to exercise type and intensity.