Antioxidant status and lipid peroxidation in hereditary haemochromatosis

Young, Ian S.; Trouton, Tom G.; Torney, J. J.; McMaster, Dorothy; Callender, M. E.; Trimble, Elisabeth R.

doi:10.1016/0891-5849(94)90041-8

Cited by 114 publications

(58 citation statements)

References 24 publications

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“…Patients with untreated hereditary hemochromatosis are known to have reduced circulating levels of antioxidant vitamins, whereas vitamin C levels return to normal when iron excess has been eliminated by venesection therapy. 25,26 The relationship between LPI and transferrin saturation is further documented by the results obtained in DYSH and in cirrhotic patients. Indeed, in DYSH where NTBI was detected (but without statistically significant increase), no increase of LPI was found.…”

Section: Discussionmentioning

confidence: 86%

Redox active plasma iron in C282Y/C282Y hemochromatosis

Lan

Loréal

Cohen

et al. 2005

Blood

136

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Labile plasma iron (LPI) represents the redox active component of non-transferrin-bound iron (NTBI). Its presence in thalassemic patients has been recently reported. The aim of the present study was to quantify LPI in HFE genetic hemochromatosis (GH) and to characterize the mechanisms accounting for its appearance. We studied 159 subjects subdivided into the following groups: (1) 23 with iron overloaded GH; (2) 14 with irondepleted GH; (3) 26 with dysmetabolic hepatosiderosis; (4) 33 with alcoholic cirrhosis; (5) 63 healthy controls. Both NTBI and LPI were substantially higher in patients with iron-overloaded GH than in those with iron-depleted GH or in healthy controls. LPI was significantly correlated with serum transaminase increase in this group. LPI was elevated in the alcoholic cirrhosis subgroup of severely affected patients. LPI was found essentially when transferrin saturation exceeded 75%, regardless of the etiologic condition. Transferrin saturation above 75% was related to iron overload in GH and to liver failure in alcoholic cirrhosis. LPI is present in C282Y/C282Y hemochromatosis and may be a marker of toxicity due to its potential for catalyzing the generation of reactive oxygen radicals in vivo. IntroductionUnder normal conditions, serum transferrin is 20% to 35% saturated with iron. However, the iron-binding capacity of transferrin in the plasma of iron-overloaded patients is often exceeded, leading to the appearance of non-transferrin-bound iron (NTBI). This pool of iron, which was first investigated by Hershko et al, 1 has been linked to the development of visceral iron excess and a toxic role toward the cells. 2 Experimentally, iron promotes the formation of free hydroxyl radicals via the Haber-Weiss reaction. Reactive oxygen species are in turn able to generate increased lipid peroxidation. 3,4 The accumulation of plasma NTBI has been shown in patients with thalassemia to correlate with the appearance of oxidation products and a decrease in plasma antioxidant capacity. 5 In genetic hemochromatosis, Gutteridge et al 6 reported that NTBI stimulated both the peroxidation of membrane lipids and the formation of hydroxyl radicals.The chemical form of NTBI remains poorly defined but is likely to be heterogeneous, involving both nonprotein and protein-bound forms that might or might not be chelatable, depending on the degree and source of iron overload. 7 The nonprotein ligands appear to correspond to low-molecular-weight organic compounds such as ascorbate, phosphate, carbonate, organic acids, and amino acids. Grootveld et al 8 proposed that NTBI in the plasma of a patient with genetic hemochromatosis (GH) existed apparently as iron citrate or iron-citrate-acetate ternary complexes, yet mostly in forms that are not directly chelatable by deferrioxamine. 7 The majority of NTBI component in plasma is bound to albumin. 9 Several methods have been introduced to quantify NTBI levels using different approaches. A 3-step assay system has been proposed, based on mobilization by nitrilotriacetate with inc...

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Section: Discussionmentioning

confidence: 86%

Redox active plasma iron in C282Y/C282Y hemochromatosis

Lan

Loréal

Cohen

et al. 2005

Blood

136

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“…6 Free radical production and oxidative stress play a key role in the triggering and progression of iron-overload cardiomyopathy and in acute iron toxicosis, as shown in isolated cardiomyocytes, 16,[41][42][43] papillary muscle preparations, 44 animal models, 18,21,45 and patients. 46,47 In both subacute and chronically iron-overloaded hearts, there was clear evidence of increased oxidative damage, as shown by marked increases in various lipid peroxidation products (aldehydes) and depletion of GSH (and GSHϩGSSG) levels. Iron-overloaded mice had marked elevations in unsaturated (MDA and HNE) and saturated (HEX) aldehydes in the heart and plasma.…”

Section: Discussionmentioning

confidence: 99%

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

et al. 2004

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Background-Iron overload has an increasing worldwide prevalence and is associated with significant cardiovascular morbidity and mortality. Elevated iron levels in the myocardium lead to impaired systolic and diastolic function and elevated oxidative stress. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca 2ϩ channels. Thus, we hypothesized that this agent would reduce the cardiovascular effects of iron overload. Methods and Results-Iron-overloaded mice were generated by intraperitoneal injection of iron either chronically (5 days per week for 13 weeks) or subacutely (5 days per week for 4 weeks). Iron overload causes increased mortality, elevated oxidative stress, systolic and diastolic dysfunction, hypotension, and bradycardia. Taurine supplementation increased myocardial taurine levels by 45% and led to reductions in mortality and improved cardiac function, heart rate, and blood pressure in iron-overloaded mice. Histological examination of the myocardium revealed reduced apoptosis and interstitial fibrosis in iron-overloaded mice supplemented with taurine. Taurine mediated reduced oxidative stress in iron-overloaded mice along with attenuation of myocardial lipid peroxidation and protection of reduced glutathione level. Conclusions-These results demonstrate that treatment with taurine reduces iron-mediated myocardial oxidative stress, preserves cardiovascular function, and improves survival in iron-overloaded mice. The role of taurine in protecting reduced glutathione levels provides an important mechanism by which oxidative stress-induced myocardial damage can be curtailed. Taurine, as a dietary supplement, represents a potential new therapeutic agent to reduce the cardiovascular burden from iron-overload conditions.

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“…However, there are several clinical examples in which high levels of endogenous iron may occur, associated with depleted levels of plasma vitamin C, namely, in thalassemia (Cohen et al, 1981), in haemochromatosis (Young et al, 1994), and in iron overload in Bantu tribesman (Nienhuis, 1981). Supplementation with vitamin C in these cases has been reported to produce deterioration in left ventricular function (Nienhuis, 1981), and rapid progression of conditions such as congestive cardiomyopathy, haemochromatosis (McLaren et al, 1982) and haemolytic diseases, for example, paroxysmal nocturnal hemoglobinuria (Iwamoto et al, 1994) and glucose-6-phosphate dehydrogenase de®ciency (Campbell et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

Yang

Kelly

et al. 1999

Eur J Clin Nutr

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Objective: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. Design: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mgad vitamin C. Setting: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. Subjects: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. Interventions: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mgad) and either 60 mgad (Group A) or 260 mgad (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and b-carotene levels) in both studies. Samples from the ®rst study were analysed for the susceptibility of LDL isolated from plasma to Cu 2 -induced oxidation and samples from the second for platelet function. Results: Transferrin-bound iron was signi®cantly increased (P`0.05) at 12 wk, in Group A subjects (from 14.9 AE 5.3 mmolal to 19.5 AE 2.3 mmolal; mean AE s.d.; n 19), whereas those in Group B showed a signi®cant increase (P`0.05) after 6 wk (from 15.8 AE 4.5 mmolal to 20.4 AE 6.6 mmolal; n 19) which decreased at 12 wk (16.3 AE 5.0 mmolal). Plasma total ascorbate signi®cantly increased from an initial level of 59.3 AE 21.3 mmolal to 87.6 AE 29.0 mmolal after 6 wk and 81.7 AE 11.4 mmolal after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0 AE 24.8 mmolal to 77.2 AE 13.2 mmolal). Plasma a-tocopherol concentrations were signi®cantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2 AE 5.7 mmolal Group A and 23.4 AE 5.3 mmolal Group B to 26.3 AE 5.5 mmolal and 25.7 AE 4.7 mmolal respectively at 12 wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was signi®cantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0 AE 14.8 min to 97.2 AE 16.9 min; n 9). Platelet sensitivity to ADP-induced aggregation was signi®cantly decreased (P`0.05) by 12 wk in Group A (from EC 50 2.3 AE 1.3 mM to 3.7 AE 2.2 mM; n 10), whereas those receiving higher vitamin C showed a signi®cant decrease (P`0.05; from EC 50 1.9 AE 0.6 mM to 3.1 AE 1.8 mM) after 6 wk which subsequently increased towards presupplemental levels (2.6 AE 1.6 mM). Platelets from the latter subjects showed a signi®cant reduction in ADP-induced ATP secretion at both 6 wk and 12 wk. Conclusion: The results show modest bene®cial effects on LDL oxidation and platelet function following supplementatio...

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Antioxidant status and lipid peroxidation in hereditary haemochromatosis

Cited by 114 publications

References 24 publications

Redox active plasma iron in C282Y/C282Y hemochromatosis

Redox active plasma iron in C282Y/C282Y hemochromatosis

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

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