Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients

Abstract

Abstract. Thalassemia and sickle-cell anemia (SCA) present a major public health problem in countries where the number of carriers and affected individuals is high. As a result of the abnormalities in hemoglobin production, cells of thalassemia and SCA patients exhibit oxidative stress, which ultimately is responsible for the chronic anemia observed. Therefore, identification of compounds exhibiting both antioxidant and hemoglobin-inducing activities is highly needed. Our results demonstrate resveratrol to be such a compound. This was shown both in the human K562 cell line, as well as in erythroid precursors derived from normal donors and β-thalassemia patients. Resveratrol was shown to exhibit antioxidant activity and to stimulate the expression of the γ-globin genes and the accumulation of fetal hemoglobin (HbF). To the best of our knowledge, this is the first report pointing to such a double effect of resveratrol. Since this natural product is already marketed as an antioxidant, future investigations should concentrate on demonstrating its potential to augment HbF production in experimental animal models (e.g., thalassemia and SCA mice) as well as in patients. We believe that the potential of clinical use of resveratrol as an antioxidant and HbF stimulator may offer a simple and inexpensive treatment to patients.

Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin

“…To verify the effects of different erythroid inducers on K562 cells expressing high levels of BCL11A-XL, K562 and K562(BCL11A-XL) clone 12 cells were treated with hydroxyurea [40] , resveratrol [17] , butyric acid [15] , 1-octylthymine [41] , rapamycin [18] , and mithramycin 35 , 36 , 37 ( Fig. 4 ).…”

“…Cell growth was studied using a Z2 Coulter Counter (Beckman Coulter, Fullerton, CA). Human primary erythroid precursor cells (ErPCs) were isolated and cultures performed as described 17 , 18 , 34 , 35 , 36 . After 7 days of cell culture phase II, cells were treated for additional 5 days with MTH.…”

“…This is supported by the fact that hydroxyurea, a powerful inducer of differentiation and HbF, is able to ameliorate the clinical parameters of β-thalassemia and SCA patients and, for this reason, has been used in several experimental trials and patient clinical management [12] . However, because of the expected side effects of HU, novel HbF inducers are of great interest in studies aimed at developing novel therapeutic options for β-thalassemia 15 , 16 , 17 , 18 .…”

Physiology and pathophysiology of iron in hemoglobin-associated diseases

“…There is also evidence from clinical observations that oxidative stress shortens the survival of mature red cells and induces apoptosis of red cell progenitors [192–196]. The red cell half life in iron-deficient patients with SCD is reduced from 15.9 days to 5.2 days when the iron deficiency is treated [197], a finding that was later corroborated by inducing iron deficiency in patients with SCD and showing increased survival, increased hemoglobin and decreased hemolysis [198].…”

Erythroid differentiation ability of butyric acid analogues: Identification of basal chemical structures of new inducers of foetal haemoglobin

“…3) (Fibach et al, 2006 andBianchi et al, 2001) and to evaluate the haemoglobin production by HPLC (Fig. 4) (Fibach et al, 2012), before the analysis of its activity using erythroid precursors from β-thalassaemia patients (Fig. 5).…”