Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia

Abstract

Background: Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. Objectives: This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. Methods: The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. Results: Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. Conclusion: SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease.

Increased oxidative stress alters nucleosides metabolite levels in sickle cell anemia

“…In our study, the serum levels of TBARS levels was significantly elevated in SCA patients. This is in agreement with previous studies where index of lipid peroxidation was reported to be increased in SCA patients [61][62][63]. RBCs are particularly susceptible to peroxidative damage because they contain hemoglobin, which has one of the powerful catalysts (Fe 2+ ) for initiation of peroxidative reaction [64].…”

Albuminuria, serum antioxidant enzyme levels and markers of hemolysis and inflammation in steady state children with sickle cell anemia

“…This observation is similar to previous reports from Nigeria [8], Egypt [9] and Qatar [5]. The decrease in antioxidant enzyme levels and activity could be explained by their susceptibility to ROS-induced oxidation [13, 14].…”

“…Sickling and subsequent hemolysis and anemia increase superoxide anion and other reactive oxygen species (ROS) production and impair ROS scavenging enzymes levels and activity in SCA patients [1]. Low ROS scavenging enzymes activity, due to either low intake of vitamins or impaired synthesis of enzymes because of cofactors deficiency [4], is thought to play the main role in the pathogenesis of oxidative stress-induced vascular complications and microalbuminuria [5]. Indeed, lower activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as altered levels of enzyme cofactors such as zinc, copper, selenium and iron have been reported in SCA patients without and with microalbuminuria [5].…”

“…Low ROS scavenging enzymes activity, due to either low intake of vitamins or impaired synthesis of enzymes because of cofactors deficiency [4], is thought to play the main role in the pathogenesis of oxidative stress-induced vascular complications and microalbuminuria [5]. Indeed, lower activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as altered levels of enzyme cofactors such as zinc, copper, selenium and iron have been reported in SCA patients without and with microalbuminuria [5]. The knowledge of the association of microalbuminuria with oxidative stress could be of therapeutic interest.…”

Two-photon microscopy imaging of oxidative stress in human living erythrocytes

“…On the other hand, the powerful antioxidant capacity of the whole blood provided by non-enzymatic and enzymatic antioxidants is contained predominantly in circulating RBCs, which allows them to maintain the oxidant/antioxidant balance in the organism [6]. However, different pathological conditions may not only trigger uncontrolled ROS generation but also lead to the alterations in the RBCs antioxidant enzyme activities and/or levels [7][8][9]. The above-mentioned circumstances show the benefits of studying oxidative stress in RBCs in pathological conditions.…”