Oxidative stress and depletion of serum antioxidant capacity in β-Thalassemia major: Role of non-transferrin-bound iron

M. D. Cappellini, D. Tavazzi, G. Cighetti, L. Duca, S. Sala, L. Bortone, G. Fiorelli

Research output: Contribution to journalArticle

Abstract

Iron-related oxidative reactions and peroxidative tissue injury are described in transfused thalassemia major (TM) patients. In this condition, an increase of toxic nontransferrin-bound iron (NTBI) has been reported. Non-enzimatic antioxidants are important parameters to assess antioxidant status in thalassemia and in other conditions associated to secondary iron overload. To clarify the role of NTBI in the generation of oxidative stress and the role of natural antioxidants in counteracting pro-oxidant effects of 'free'iron, we studied 21 transfusion-dependent β-TM patients and 10 healthy adults. Blood was obtained after at least 48 hours from the last deferoxamine infusion and just before transfusion. NTBI was measured in fresh serum by HPLC after nitrilotriacetic acid chelation and ultrafiltration. Lipid peroxidation was evaluated as serum free/total malonyl-dialdehyde (MDA) by selected ion monitoring gas chromatography-mass spectrometry. Total radicaltrapping antioxidant parameter (TRAP) was tested in serum by fluorescent monitoring of Trolox-induced lag phase using dichlorofluorescin-diacetate. Iron status parameters, albumin, bilirubin and uric acid, were from clinical laboratory procedures. Over-normal amounts of NTBI (p<.0001), free (p<.0001) and total MDA (p<.0384) were observed in TM patients compared to controls. In the TM group, NTBI negatively correlated with TRAP (R= -.477, p= .0287) and albumin (R= -.565, p= .0075), while positively correlated with total MDA (R= .453, p= .0392). In all the subjects evaluated, NTBI resulted positively correlated with both free (n=21 + 10, R= .669, p<.0001) and total MDA (R= .524, p= .0025), and showed negative correlations with TRAP (R= -.435, p= .0142). NTBI, a prooxidant compound in β-thalassemia serum, may contribute to oxidative stress and tissue damage; this may be enhanced by severe depletion of antioxidants and GSH instability. NTBI seems to be determinant for the increased lipid peroxidation through an impairment of the overall antioxidant capacity. Natural antioxidants such as albumin, ceruloplasmin and urates are unlikely themselves to efficiently counteract free radical damage through aspecific interactions with low-molecular-weight iron in the absence of a proper chelation therapy. Potential benefits in TM treatment can be expected from supplementation of lipid-soluble vitamins, flavonoids or other radical scavengers.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART II
Publication statusPublished - 2000

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Oxidative stress
beta-Thalassemia
Oxidative Stress
Iron
Antioxidants
Serum
Albumins
Thalassemia
Uric Acid
Chelation
Lipid Peroxidation
Lipids
Nitrilotriacetic Acid
Chelation Therapy
Clinical laboratories
Tissue
Ceruloplasmin
Deferoxamine
Iron Overload
Poisons

ASJC Scopus subject areas

  • Hematology

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Oxidative stress and depletion of serum antioxidant capacity in β-Thalassemia major : Role of non-transferrin-bound iron. / Cappellini, M. D.; Tavazzi, D.; Cighetti, G.; Duca, L.; Sala, S.; Bortone, L.; Fiorelli, G.

In: Blood, Vol. 96, No. 11 PART II, 2000.

Research output: Contribution to journalArticle

Cappellini, M. D. ; Tavazzi, D. ; Cighetti, G. ; Duca, L. ; Sala, S. ; Bortone, L. ; Fiorelli, G. / Oxidative stress and depletion of serum antioxidant capacity in β-Thalassemia major : Role of non-transferrin-bound iron. In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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T2 - Role of non-transferrin-bound iron

AU - Cappellini, M. D.

AU - Tavazzi, D.

AU - Cighetti, G.

AU - Duca, L.

AU - Sala, S.

AU - Bortone, L.

AU - Fiorelli, G.

PY - 2000

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N2 - Iron-related oxidative reactions and peroxidative tissue injury are described in transfused thalassemia major (TM) patients. In this condition, an increase of toxic nontransferrin-bound iron (NTBI) has been reported. Non-enzimatic antioxidants are important parameters to assess antioxidant status in thalassemia and in other conditions associated to secondary iron overload. To clarify the role of NTBI in the generation of oxidative stress and the role of natural antioxidants in counteracting pro-oxidant effects of 'free'iron, we studied 21 transfusion-dependent β-TM patients and 10 healthy adults. Blood was obtained after at least 48 hours from the last deferoxamine infusion and just before transfusion. NTBI was measured in fresh serum by HPLC after nitrilotriacetic acid chelation and ultrafiltration. Lipid peroxidation was evaluated as serum free/total malonyl-dialdehyde (MDA) by selected ion monitoring gas chromatography-mass spectrometry. Total radicaltrapping antioxidant parameter (TRAP) was tested in serum by fluorescent monitoring of Trolox-induced lag phase using dichlorofluorescin-diacetate. Iron status parameters, albumin, bilirubin and uric acid, were from clinical laboratory procedures. Over-normal amounts of NTBI (p<.0001), free (p<.0001) and total MDA (p<.0384) were observed in TM patients compared to controls. In the TM group, NTBI negatively correlated with TRAP (R= -.477, p= .0287) and albumin (R= -.565, p= .0075), while positively correlated with total MDA (R= .453, p= .0392). In all the subjects evaluated, NTBI resulted positively correlated with both free (n=21 + 10, R= .669, p<.0001) and total MDA (R= .524, p= .0025), and showed negative correlations with TRAP (R= -.435, p= .0142). NTBI, a prooxidant compound in β-thalassemia serum, may contribute to oxidative stress and tissue damage; this may be enhanced by severe depletion of antioxidants and GSH instability. NTBI seems to be determinant for the increased lipid peroxidation through an impairment of the overall antioxidant capacity. Natural antioxidants such as albumin, ceruloplasmin and urates are unlikely themselves to efficiently counteract free radical damage through aspecific interactions with low-molecular-weight iron in the absence of a proper chelation therapy. Potential benefits in TM treatment can be expected from supplementation of lipid-soluble vitamins, flavonoids or other radical scavengers.

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