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E J Bechara

Publications and source records attributed to E J Bechara.

At least 73 records · Page 4Linked to original sources
PubMed1993

5-aminolevulinic acid induces lipid peroxidation in cardiolipin-rich liposomes.

5-Aminolevulinic acid (ALA), a heme precursor accumulated in lead poisoning and acute intermittent porphyria, is known to undergo metal-catalyzed aerobic oxidation to yield reactive oxygen species. In phosphatidylcholine:cardiolipin (80:20) liposomes ALA (0.1-3.0 mM) promoted lipid peroxidation as evaluated by the formation of conjugated dienes and 2-thiobarbituric-reactive substances (TBARS). TBARS formation was dependent on ALA concentration and incubation time. ALA-induced lipid peroxidation was associated with an increase in liposome permeability as measured by the release of encapsulated carboxyfluorescein. alpha-Tocopherol (0.1-0.5 mol %), an efficient oxyradical scavenger, inhibits lipid peroxidation and prevents carboxyfluorescein release, suggesting that the permeabilization of liposomes is mainly due to lipid peroxidation. Cardiolipin, a major component of mitochondrial inner membrane, was particularly susceptible to ALA-induced lipid peroxidation. These results may be relevant to the previously observed Ca(2+)-dependent permeabilization of the inner membrane of rat liver mitochondria promoted by external 0.1-1.0 mM ALA; this mechanism has been implicated in the pathophysiology of acute intermittent porphyria and lead poisoning.

Aminolevulinic Acid↗
PubMed1992

Calcium-dependent mitochondrial oxidative damage promoted by 5-aminolevulinic acid.

Swelling of isolated rat liver mitochondria is shown to be induced by metal-catalyzed 5-aminolevulinic acid (ALA) aerobic oxidation, a putative endogenous source of reactive oxygen species (ROS), at concentrations as low as 50-100 microM. In this concentration range, ALA is estimated to occur in the liver of acute intermittent porphyria patients. Removal of Ca2+ (10 microM) from the suspension of isolated rat liver mitochondria by added EGTA abolishes both the ALA-induced transmembrane-potential collapse and mitochondrial swelling. Prevention of the ALA-induced swelling by addition of ruthenium red prior to mitochondrial energization by succinate demonstrates the deleterious involvement of internal Ca2+. Addition of MgCl2 at concentrations higher than 2.5 mM, prevents the ALA-induced mitochondrial swelling, transmembrane potential collapse and Ca2+ efflux. This indicates that Mg2+ protects against the mitochondrial damage promoted by ALA-generated ROS. The ALA-induced mitochondrial damage might be a key event in the liver mitochondrial damage of acute intermittent porphyria patients reported elsewhere.

Aminolevulinic Acid↗
PubMed1992

Are dioxetanes chemiluminescent intermediates in lipoperoxidation?

Ultraweak chemiluminescence arising from lipoperoxidation has been attributed by several authors to the radiative deactivation of singlet oxygen and triplet carbonyl products. The latter emitters have been suggested to come from annihilation of RO. and ROO. radicals as well as from the thermolysis of dioxetane intermediates formed by (2 + 2) cycloaddition of 1O2 to polyunsaturated fatty acids. This article questions possible dioxetane intermediacy in lipoperoxidation, as the literature clearly states that addition of 1O2 to alpha-hydrogen-containing alyphatic olefins yields only the corresponding allylic hydroperoxides. These compounds may undergo dark thermal or Lewis acid-assisted decomposition to the same product obtained from dioxetane cleavage. Here, reexamining the chemiluminescence properties of dioxygenated tetramethylethylene and linoleic acid and comparing them with those of tetraethyldioxetane, a hindered dioxetane, we corroborate the literature information that only steric hindrance leads to dioxetane formation upon singlet oxygen addition to electron-poor olefins, albeit in very low yields. Proton nuclear magnetic resonance (1H-NMR) analysis, quenching by dioxygen and energy transfer studies to 9,10-dibromoanthracene, as well as gas chromatography (GC) analysis of triphenylphosphine-treated and untreated photo- and chemically dioxygenated olefins support our final conclusion that dioxetane formation during lipoperoxidation can be safely excluded on the basis of the data presently available.

Alcohols↗
PubMed1992

5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats.

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.

Aminolevulinic Acid↗
PubMed1991

Free radicals involvement in neurological porphyrias and lead poisoning.

Porphyrias are inherited and acquired diseases of erythroid or hepatic origin, in which there are defects in specific enzymes of the heme biosynthetic pathway. In patients with intermittent acute porphyria and lead poisoning the erythrocytic activities of superoxide dismutase and glutathione peroxidase are reported to be increased. Our studies demonstrated that d-aminolevulinic acid, a heme precursor accumulated in both diseases, undergoes enolization at pH less than 7.0 before it autoxidizes. The autoxidation of d-aminolevulinic acid, in the presence or absence of oxyhemoglobin has been proposed as a source of oxy and carbon-centred radicals in the cells of intermittent acute porphyria and saturnism carriers. Thus, the increased levels of antioxidant enzymes can be viewed as an intracellular response against the deleterious effects of these extremely reactive species.

Aminolevulinic Acid↗
PubMed1991

Damage to rat liver mitochondria promoted by delta-aminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphyria and lead-poisoning.

delta-Aminolevulinic acid is a heme precursor accumulated in acute intermittent porphyria and lead-poisoning, which supposedly triggers the typical clinical expression associated with these diseases. Considering that: (i) erythrocyte anti-oxidant enzymes are abnormally high in patients with both disorders and (ii) delta-aminolevulinic acid autoxidation generates reactive oxygen species, a possible contribution of reactive oxygen species in the pathophysiology of these disorders is explored here. Evidence is provided that delta-aminolevulinic acid (2-15 mM) induces damage to isolated rat liver mitochondria. Addition of delta-aminolevulinic acid disrupts the mitochondrial membrane potential, promotes Ca2+ release from the intramitochondrial matrix and releases the state-4 respiration, thus enhancing the permeability of the membrane to H+. The lesion was abolished by catalase, superoxide dismutase (both enzymes inhibit delta-aminolevulinic acid autoxidation) and ortho-phenanthroline, but not by mannitol; added H2O2 induces damage poorly. These results suggest the involvement of deleterious reactive oxygen species formed at particular mitochondrial sites from transition metal ions and delta-aminolevulinic acid-generated peroxide and/or superoxide species. These observations might be compatible with previous work showing hepatic mitochondrial damage in liver biopsy samples of acute intermittent porphyria patients.

Aminolevulinic Acid↗
PubMed1991

Are free radicals involved in lead poisoning?

1. The enolamine form of 5-aminolaevulinic acid (ALA), a haem precursor that accumulates in lead poisoning and in acute intermittent porphyria (AIP), undergoes fast autoxidation at slightly alkaline pH with concomitant generation of reactive oxygen species. 2. The transmembrane potential, Ca2+ ion fluxes and state-4 respiratory rate, of isolated rat liver mitochondria are severely affected by mM addition of ALA; the toxic role of ALA-produced oxygen radicals was demonstrated by use of appropriate scavengers. 3. Induction of superoxide dismutase biosynthesis in lead-exposed workers, in AIP carriers and in ALA-treated rats, is viewed as a protective response against oxygen radical toxicity. 4. 5-Aminolaevulinic acid-generated oxygen radicals, together with Pb-stimulated Fe-dependent lipid peroxidation, might be involved in the aetiology of the neuropsychiatric manifestations of both plumbism and acute intermittent porphyria.

Animals↗
PubMed1989

Free radical generation during delta-aminolevulinic acid autoxidation: induction by hemoglobin and connections with porphyrinpathies.

delta-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and saturnism, undergoes autoxidation leading to ammonium ion and probably the corresponding alpha-ketoaldehyde. This reaction is accelerated by addition of oxyhemoglobin (oxyHb) and other iron complexes. OxyHb is concomitantly oxidized to metHb; the apparent second-order rate constant of oxyHb/ALA coupled oxidation is ca. 10 M-1 min-1.1H NMR and uv spectral studies suggest that ALA undergoes enolization before consuming the dissolved oxygen. Spin-trapping experiments demonstrate formation of both the hydroxyl radical and a substrate-derived carbon-centered radical during ALA oxidation. Generation of active oxygen species by ALA might be related to the neuropathy associated to some acquired and inherited porphyrinpathies.

Aminolevulinic Acid↗
PubMed1986

Generation of active oxygen species during coupled autoxidation of oxyhemoglobin and delta-aminolevulinic acid.

The conversion of oxyhemoglobin to methemoglobin has been shown via spectrophotometric, circular dichroism and polarographic studies to be accelerated by delta-aminolevulinic acid, a major heme-precursor accumulated in a number of heme-linked pathologies. Concomitantly, delta-aminolevulinic acid undergoes aerobic oxidation. The intermediacy of oxygen radicals in these processes was evidenced by the inhibitory effect of catalase, superoxide dismutase and mannitol. These results are relevant to the exacerbated production of active oxygen species in intermittent acute porphyria and saturnism carriers.

Aminolevulinic Acid↗
PubMed1986

Ruthenium(II) tris(bipyridyl) ion as a luminescent probe for oxygen uptake.

The present work describes an alternative technique for following the rate of oxygen uptake by chemical and enzymatic systems. This method is based on spectrofluorometric monitoring of the well-known quenching effect of molecular oxygen on the emission of the photoexcited [Ru(bpy)3]2+ ion, added to the reaction mixtures. The rate of oxygen consumption determined using the present method agrees with that obtained by conventional polarographic techniques in all of the following systems: ascorbate/Cu2+, glucose/glucose oxidase (EC 1.1.3.4), and propanal/horseradish peroxidase (EC 1.11.1.7); in the last case, agreement was observed both in the presence and absence of serum albumin and of chloroplasts. Spectrofluorometric data for amphotericin autoxidation in dimethyl sulfoxide are in accord with the rate of decay of the ESR signal of a spin trap added to the reaction mixture. The advantages and limitations of the present spectrofluorometric technique relative to conventional polarographic monitoring of dissolved oxygen are discussed.

2,2'-Dipyridyl↗
PubMed1986

Chemiluminescent aerobic oxidation of protein adducts with glycolaldehyde catalyzed by horseradish peroxidase.

Horseradish peroxidase (EC 1.11.1.7) is shown to catalyze the aerobic oxidation of lysozyme, bovine serum albumin, and protamine adducts with glycolaldehyde at physiological pH. This reaction is accompanied by light emission, which is attributed to the generation of triplet species. The intensity of chemiluminescence is enhanced by addition of chlorophyll alpha solubilized in Brij 35. A role of electronically excited species in deleterious and pathological processes associated with formation of Schiff-type adducts is suggested, with emphasis on the case of alcohol-induced liver injury.

Acetaldehyde↗
PubMed1986

Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients.

Activities of superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9) in erythrocytes were evaluated in 50 schizophrenic and 20 manic-depressive patients, who were or were not being treated with different neuroleptic drugs, and results were compared with those for 58 normal individuals. Neuroleptic-treated and untreated schizophrenic patients showed similar activities of superoxide dismutase, about 60% higher than those found in normal individuals (p less than 0.001). In manic-depressive patients treated with either lithium (n = 8) or lithium plus neuroleptic drugs (n = 12), superoxide dismutase activities were increased by about 40% over those of normal subjects (p less than 0.001). Significantly abnormal activities of glutathione peroxidase were found only in the sub-group of schizophrenic women. These results are interpreted in terms of active oxygen species involvement in the psychiatric manifestations.

Adult↗
PubMed1985

Oxygen toxicity related to exposure to lead.

We evaluated superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9) activities in the erythrocytes of lead-exposed and nonexposed workers from distinct industries localized in the State of São Paulo, Brazil. Concentrations of either lead or protoporphyrin IX, or both, in blood were used to indicate the extent of exposure. In all cases, values for superoxide dismutase were significantly higher in the exposed workers. The dose-response relationship between this enzyme and lead concentrations was roughly linear for the workers with greater than 40 micrograms of lead per 100 g of blood. Except for the sample from one of the industries, the corresponding glutathione peroxidase activities were also significantly higher in lead-exposed workers. These data, together with those previously found for patients with intermittent acute porphyria, suggest that in both groups the accumulation of heme precursors is connected to the exacerbated production of activated oxygen species.

Adolescent↗
PubMed1980

Hemin-catalyzed generation of triplet acetone.

Hemin can substitute for horseradish peroxidase as a catalyst for the aerobic oxidation of isobutanal to acetone and formate. Previous studies have shown that the chemiphosphorescent emission observed in the enzyme-catalyzed reaction is due to the production of acetone in its triplet state. Although no chemiphosphorescence is observed with the model system (hemin), generation of triplet acetone in this system is indicated by an analysis of data for energy transfer to the 9,10-dibromoanthracene-2-sulfonate ion and for interception of the excited species by the sorbate ion, a known triplet quencher. These data are compared to those obtained with triplet acetone generated by thermal cleavage of tetramethyldioxetane in aqueous solution. The results are in agreement with the hypothesis that the quenching of triplet acetone by oxygen is less efficient in the enzyme catalyzed reaction, pointing to a protective role for the apoenzyme in that system.

Acetone↗