196,034 research outputs found
Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil
No full textMouse erythrocytes were incubated with oxidizing agents, phenylhydrazine, divicine and isouramil. With all the oxidants a rapid release of iron in a desferrioxamine (DFO)-chelatable form was seen and it was accompanied by methaemoglobin formation. If the erythrocytes were depleted of GSH by a short preincubation with diethyl maleate, the release of iron was accompanied by lipid peroxidation and, subsequently, haemolysis. GSH depletion by itself did not induce iron release, methaemoglobin formation, lipid peroxidation or haemolysis. Rather, the fate of the cell in which iron is released depended on the intracellular availability of GSH. In addition, iron release was higher in depleted cells than in native ones, suggesting a role for GSH in preventing iron release when oxidative stress is imposed by the oxidants. Iron release preceded lipid peroxidation. The latter was prevented when the erythrocytes were preloaded with DFO in such a way (preincubation with 10 mM-DFO) that the intracellular concentration was equivalent to that of the released iron, but not when the intracellular DFO was lower (preincubation with 0.1 mM-DFO). Extracellular DFO did not affect lipid peroxidation and haemolysis, suggesting again that the observed events occur intracellularly (intracellular chelation of released iron). The relevance of iron release from iron complexes in the mechanisms of cellular damage induced by oxidative stress is discussed
Allyl alcohol-induced hemolysis and its relation to iron release and lipid peroxidation
No full textAllyl alcohol administration to starved mice produced, along with liver necrosis, a high incidence (about 50%) of hemolysis. A marked decrease in erythrocyte glutathione (GSH) was seen in all the intoxicated animals. Such a decrease was significantly higher in the animals showing hemolysis. In these animals a substantial amount of malonic dialdehyde (MDA) was detected in plasma and a marked decrease in arachidonic and docosahexaenoic acids was found in erythrocyte phospholipids. These data suggest that the allyl alcohol-induced hemolysis is mediated by lipid peroxidation. In vitro studies have shown that the addition of acrolein to mouse erythrocytes produces a dramatic GSH depletion, which is followed by the appearance of lipid peroxidation and, after an additional 30 min of incubation, by the development of hemolysis. Prevention of lipid peroxidation by an antioxidant (Trolox C) or an iron chelator (desferrioxamine, DFO), prevented hemolysis even if the erythrocyte GSH level was dramatically decreased. In vitro, allyl alcohol and acrylic acid were ineffective in inducing GSH depletion, lipid peroxidation and hemolysis. Studies of possible induction of lipid peroxidation in erythrocytes showed that a progressive increase in "free" (desferal chelatable) iron occurs in the erythrocytes during the incubation with acrolein. It seems, therefore, that a release of iron from iron-containing complexes occurs in acrolein-treated erythrocytes and that such "free" iron promotes lipid peroxidation. © 1989
Iron release and erythrocyte damage in allyl alcohol intoxication in mice
No full textAllyl alcohol administration in a toxic dose (1.5 mmol/kg) to starved mice causes the development of hemolysis in nearly 50% of the animals. Malonic dialdehyde (MDA) appears in plasma of the animals showing hemolysis. The treatment of mice with desferrioxamine after allyl alcohol intoxication completely prevents lipid peroxidation and hemolysis, suggesting the involvement of iron in the allyl alcohol-induced erythrocyte damage. Erythrocytes obtained from intoxicated mice before the development of hemolysis show, upon incubation, release of iron, lipid peroxidation and lysis. Studies carried out with reconstituted systems of erythrocyte lysates, containing ghosts and different fractions of erythrocyte cytosol and incubated in the presence of acrolein (the major metabolite of allyl alcohol), strongly suggest that iron is released from hemoglobin. This iron appears to promote lipid peroxidation which is accompanied by erythrocyte lysis. Thus, the allyl alcohol-induced hemolysis appears to be a model for iron delocalization from iron stores
Iron released from an erythrocyte lysate by oxidative stress is diffusible and in redox active form
No full textThe incubation of a ghost-free erythrocyte lysate with the oxidizing agent phenylhydrazine resulted in both methemoglobin formation and release of iron in a desferrioxamine (DFO)-chelatable form. The released iron was diffusible, as shown by a dialysis carried out simultaneously with the incubation. When the dialysate was added to erythrocyte ghosts or to microsomes from liver or brain, lipid peroxidation developed in the membranes, indicating that the diffusible iron was in a redox active form. The addition of ATP to the lysate markedly increased both iron diffusion and lipid peroxidation in the membranes subsequently added to the dialysate. The possible implication of these data in some well known pathologies is discussed. © 1993
Evidence for aldehydes bound to liver microsomal protein following CCl4 or BrCCl3 poisoning
No full textSince it has been demonstrated in previous studies that peroxidation of liver microsomal lipids leads to the production of aldehydes provided with cytopathological activities-namely 4-hydroxyalkenals-evidence was searched for aldehydes bound to microsomal protein in in vivo conditions (CCl4 and BrCCl3 intoxications) in which peroxidation of lipids of hepatic endoplasmic reticulum had been demonstrated previously. The spectrophotometric analysis of 2,4-dinitrophenylhydrazine-treated non-lipoidal residues of liver microsomes from the intoxicated rats shows absorption spectra similar to those observed for the dinitrophenylhydrazones formed in the reaction of alkenals with -SH groups of proteins or low molecular weight thiols. Similar spectra, although magnified from a quantitative point of view, were obtained either with liver microsomes allowed to react with synthetic 4-hydroxynonenal or with liver microsomes peroxidized in the NADPH-Fedependent system. A time-course study of microsomal lipid peroxidation shows that the amount of 2,4-dinitrophenylhydrazine-reacting groups in the non-lipoidal residue of liver microsomes increases with the incubation time and is correlated to the amount of thiobarbituric acid-reacting products formed in the incubation mixture. In both the in vivo conditions (CCl4 and BrCCl3 intoxications) the amount of 2,4-dinitrophenylhydrazine-reacting groups in the non-lipoidal residue of liver microsomes increases from 15 min up to 2 h after poisoning and is higher, in every instance, in the BrCCl3-intoxicated animals compared to the CCl4-poisoned ones. Experiments carried out to ascertain the reliability of the spectrophotometric detection of protein-bound alkenals showed that in the in vitro system in which liver microsomes are allowed to react with 4-hydroxynonenal there is a good agreement between the binding value that can be calculated from the absorption spectrum and the binding value obtained by using labelled 4-hydroxynonenal. © 1982
A study of the relationships between carbon tetrachloride induced lipid peroxidation and liver damage in rats pretreated with vitamin E
No full textIron release, lipid peroxidation, and morphological alterations of erythrocytes exposed to acrolein and phenylhydrazine
No full textIron is released in a free [desferrioxamine (DFO)-chelatable] form in mouse erythrocytes incubated with the oxidizing agents acrolein and phenylhydrazine or in erythrocytes drawn from allyl alcohol-intoxicated mice. The release is accompanied by peroxidation of membrane lipids when the cells are depleted of glutathione. Lipid peroxidation is always followed by the lysis of the cells. The release of iron is also accompanied by methemoglobin formation, but the extent of the release does not correlate with the level of methemoglobin production. The addition of DFO to the incubation mixture or the preincubation of the erythrocytes with DFO in millimolar concentrations completely prevents both lipid peroxidation and hemolysis while not significantly changing the level of iron release. Morphological studies carried out with scanning electron microscopy showed a number of alterations in the shape of the incubated erythrocytes, including echinocyte transformation and the appearance of codocyte, stomatocyte, and cnizocyte like forms. These alterations were more prominent with increasing lipid peroxidation and hemolysis, even if occurring in their absence. On the contrary, the appearance of pits and holes was strictly associated with lipid peroxidation and lysis. © 1994 Academic Press, Inc
Iron mobilization from crocidolite as enhancer of collagen content in rat lung fibroblasts
No full textAsbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain. There is increasing evidence that iron from asbestos is responsible for many of its effects. In this paper, we investigated the effect of iron mobilized from crocidolite asbestos on collagen content in rat lung fibroblast cultures under serum-free conditions. Crocidolite (2, 4, 6 microg/cm2 well) increased collagen content in a dose-dependent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs controls). This effect was specific for collagen, since it did not alter total protein content and was inhibited by the iron chelator deferoxamine (DFO). Preincubation of crocidolite with citrate (1 mM) for 48 hr resulted in iron mobilization (51 microM) and increased collagen production (>3-fold) in treated cells. These effects occurred without the intervention of serum factors. The absence of cell damage, proliferation or lipid peroxidation leads to the supposition that iron from crocidolite per se may act as a profibrogenic agent. Although the in vivo participation of other cells and factors cannot be excluded, we conclude that iron released from crocidolite plays a role in collagen increase occurring during asbestosis
Acrolein or phenylhydrazine-induced iron release and its relationships with oxidative damage in erythrocytes.
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