Mechanism of <i>in vitro</i> heme‐induced LDL oxidation: effects of antioxidants

Klouche, Kada; Moréna, Marion; Canaud, Bernard; Descomps, Bernard; Béraud, J. J.; Cristol, Jean‐Paul

doi:10.1111/j.1365-2362.2004.01395.x

Cited by 45 publications

(31 citation statements)

References 42 publications

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“…Secondly, it has been shown that iron alone or in combination with vitamin C and hydrogen peroxide is only a weak inducer of LDL oxidation. By contrast, the association of heme and hydrogen peroxide could induce LDL oxidation via the generation of perferryl radical [25,26] . Duration of dialysis treatment which was not equal within centers (patients from St L being on dialysis for longer time) also influenced oxidizability of LDL.…”

Section: Discussionmentioning

confidence: 99%

Regional Variations of Low-Density Lipoprotein Oxidizability in Hemodialysis Patients May Explain Discrepancies in Interventional Therapy on Oxidative Profile

Moréna¹,

Gausson

Mothu

et al. 2008

Blood Purif

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Background/Aims: This study aimed at evaluating oxidative stress (OS) markers (i) in a cross-sectional study of hemodialysis (HD) patients to investigate potential regional effects of these markers and (ii) in a prospective crossover study to evaluate vitamin E-coated membrane (VE) effects. Methods: At baseline, OS parameters including low-density lipoprotein (LDL) oxidizability were measured in HD patients from five dialysis facilities. Patients were then randomly assigned to two treatment groups: group I patients (n = 33) switching to VE, and group II patients (n = 29) still using reference polysulfone (PS) membrane. After 3 months, patients were switched from VE to PS and vice versa for 6 months. The same OS parameters were measured after each period. Results: At baseline, the cross-sectional analysis of LDL oxidizability showed a regional effect. By contrast, the crossover study did not show beneficial effects of VE on this parameter. Conclusion: Regional variations of LDL oxidizability in HD patients exist and may explain discrepancies in interventional therapy on OS.

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Section: Discussionmentioning

confidence: 99%

Regional Variations of Low-Density Lipoprotein Oxidizability in Hemodialysis Patients May Explain Discrepancies in Interventional Therapy on Oxidative Profile

Moréna¹,

Gausson

Mothu

et al. 2008

Blood Purif

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“…Recently, it has been suggested that intact hemin can interact with H 2 O 2 to mediate toxicity in cells (Robinson et al, 2009). Intact hemin can engage directly in Fenton reactions with H 2 O 2 and generate hydroxyl radicals (Huffman et al, 2000), and hemin can also initiate lipid peroxidation in the presence of H 2 O 2 (Gutteridge and Smith, 1988;Klouche et al, 2004). This study demonstrated that exogenous H 2 O 2 potentiated hemin toxicity, and this additional cell loss was prevented by PHEN.…”

Section: Discussionmentioning

confidence: 69%

“…However, we consider this possibility unlikely since Trolox, which is able to attenuate lipid peroxidation (Balla et al, 1991;Klouche et al, 2004), did not protect astrocytes from hemin toxicity in the absence of excess H 2 O 2 . Alternately, hemin may aggregate in regions of the cell that are more likely to induce cell death when damaged.…”

Section: Discussionmentioning

confidence: 96%

The metabolism and toxicity of hemin in astrocytes

Dang

Bishop

Dringen

et al. 2011

Glia

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Hemin is cytotoxic, and contributes to the brain damage that accompanies hemorrhagic stroke. In order to better understand the basis of hemin toxicity in astrocytes, the present study quantified hemin metabolism and compared it to the pattern of cell death. Heme oxygenase-1 (HO-1) expression was first evident after 2 h incubation with hemin, with maximal expression being observed by 24 h. Despite the induction of HO-1, it was found that the proportion of hemin metabolized by astrocytes remained fairly constant throughout the 24 h period, with 70-80% of intracellular hemin remaining intact. A period of cell loss began after 2 h exposure to hemin, which gradually increased in severity to reach a maximum by 24 h. This cell loss could not be attenuated by the iron chelator, 1,10-phenanthroline, or by several antioxidant compounds (Trolox, N-acetyl-L-cysteine and N-tert-butyl-α-phenylnitrone), indicating that the mechanism of hemin toxicity does not involve iron. While these results make it unlikely that hemin toxicity is due to interactions with endogenous H(2)O(2), hemin toxicity was increased in the presence of supraphysiological levels of H(2)O(2) and this increase was ameliorated by PHEN, indicating that the iron released from hemin can be toxic under some pathological conditions. However, when H(2)O(2) is present at physiological levels, the toxicity of hemin appears to be caused by other mechanisms that may involve bilirubin and carbon monoxide in this model system.

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“…The intercalation of hemin into the plasma membrane increases the sensitivity of cells to the toxicity of exogenous H 2 O 2 (see Balla et al 20 ), since the rate of lipid peroxidation is greatly accelerated by H 2 O 2 . 20,63 Once initiated, the rapid peroxidation of membrane lipids becomes an autocatalytic process that depends on the presence of hemin but does not require H 2 O 2 . 20 Despite the uncertainty regarding the mechanism(s) involved in this process, 20,61 there is general agreement that the oxidation of unsaturated lipids by hemin is most effectively prevented by radical scavenging antioxidants such as vitamin E, 20,62,63 which are known to break the progression of the radical chain reaction that causes lipid peroxidation.…”

Section: Interactions Between Hydrogen Peroxide and Heminmentioning

confidence: 99%

Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke

et al. 2009

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Hemorrhagic stroke is a common cause of permanent brain damage, with a significant amount of the damage occurring in the weeks following a stroke. This secondary damage is partly due to the toxic effects of hemin, a breakdown product of hemoglobin. The serum proteins hemopexin and albumin can bind hemin, but these natural defenses are insufficient to cope with the extremely high amounts of hemin (10 mM) that can potentially be liberated from hemoglobin in a hematoma. The present review discusses how hemin gets into brain cells, and examines the multiple routes through which hemin can be toxic. These include the release of redox-active iron, the depletion of cellular stores of NADPH and glutathione, the production of superoxide and hydroxyl radicals, and the peroxidation of membrane lipids. Important gaps are revealed in contemporary knowledge about the metabolism of hemin by brain cells, particularly regarding how hemin interacts with hydrogen peroxide. Strategies currently being developed for the reduction of hemin toxicity after hemorrhagic stroke include chelation therapy, antioxidant therapy and the modulation of heme oxygenase activity. Future strategies may be directed at preventing the uptake of hemin into brain cells to limit the opportunity for toxic interactions.

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Mechanism of in vitro heme‐induced LDL oxidation: effects of antioxidants

Cited by 45 publications

References 42 publications

Regional Variations of Low-Density Lipoprotein Oxidizability in Hemodialysis Patients May Explain Discrepancies in Interventional Therapy on Oxidative Profile

Regional Variations of Low-Density Lipoprotein Oxidizability in Hemodialysis Patients May Explain Discrepancies in Interventional Therapy on Oxidative Profile

The metabolism and toxicity of hemin in astrocytes

Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke

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