ubiquinone and beta-Thalassemia

The aim of this study was to evaluate the plasma coenzyme Q(10) (CoQ(10)) concentration, a vitamin-like substance found in every cell, which is also viewed as the most effective membrane antioxidant, of thalassemic patients and investigate the effect of chelating agents and ferritin levels on its concentration in patients with β-thalassemia major (β-TM). The study included 44 β-TM patients undergoing deferasirox (DFRA) or deferoxamine (DFO) chelation monotherapies or combined therapy with deferiprone (L1) and DFO, 20 patients with β-thalassemia (β-thal) traits and a control group of 22 healthy sex- and age-matched subjects. Complete blood counts, liver and renal function tests, lipid profiles, ferritin and plasma CoQ(10) [by high performance liquid chromatography (HPLC)] were analyzed. The mean age (14.7 ± 7.3 years; median 14.3 years) and sex (26 males, 18 females) of the β-TM patients were not statistically different from the β-thal trait patients and the control group. The plasma CoQ(10) concentration was 0.425 ± 0.136 μmol/L in β-TM patients, 0.508 ± 0.159 μmol/L in the β-thal trait patients and 0.534 ± 0.133 μmol/L in the control group. The difference was significant in both the β-TM (p < 0.001) and β-thal trait patients (p <0.05) compared to the control group. The CoQ(10) concentration was also associated with ferritin levels in β-TM patients; the β-TM patients with high ferritin levels had a lower CoQ(10) (p <0.05) concentration. Also, higher plasma CoQ(10) levels were detected in β-TM patients undergoing DFRA treatment, according to combined therapy administered (0.457 ± 0.115 vs. 0.382 ± 0.127 mg/dL respectively, p <0.05). In conclusion, both the β-thal trait and β-TM patients have lower antioxidant capacity as demonstrated by the lower CoQ(10) levels. The type of chelating agents and ferritin levels are factors effecting CoQ(10) concentration in β-TM patients.

Topics: Adolescent; Adult; Benzoates; beta-Thalassemia; Chelation Therapy; Child; Child, Preschool; Deferasirox; Deferiprone; Deferoxamine; Drug Therapy, Combination; Female; Ferritins; Humans; Iron Chelating Agents; Male; Pyridones; Treatment Outcome; Triazoles; Ubiquinone; Young Adult

Thalassemia is a group of genetic disorders resulting from different mutations in the globin gene complex and leading to an imbalance in globin synthesis. Unmatched globin chains are less stable and susceptible to oxidation. Patients with beta-thalassemia/HbE are prone to increased oxidative stress as indicated by increased lipid peroxidation product, malondialdehyde (MDA), partly because of the presence of iron in the form of heme and hemichromes released from excess globin chains and excess iron deposition in various tissues. The level of antioxidant such as glutathione is markedly decreased while activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) are increased. We have recently found that the levels of coenzyme Q(10) (CoQ(10)) are also very low in thalassemia. We therefore evaluated the oxidative stress and the antioxidants in these patients before and after supplementation with 100 mg CoQ(10) daily for 6 months. The results showed that the plasma level of CoQ(10) significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ(10) led to significant improvement of biochemical parameters of antioxidant enzymes. The antioxidant supplementation will be beneficial for thalassemia patients as adjunct therapy to increase their quality of life.

Topics: Adenosine Triphosphate; Adolescent; Adult; Antioxidants; beta-Thalassemia; Catalase; Coenzymes; Female; Glutathione; Glutathione Peroxidase; Hemoglobin E; Humans; Male; Malondialdehyde; Oxidative Stress; Superoxide Dismutase; Thailand; Ubiquinone

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.

Topics: Adolescent; Adult; Antioxidants; beta-Thalassemia; Bilirubin; Carotenoids; Catecholamines; Child; Fatty Acids; Female; Ferritins; Humans; Iron; Lipid Peroxidation; Male; Oxidative Stress; Serotonin; Sulfhydryl Compounds; Ubiquinone; Uric Acid; Vitamins