In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-Dimercaptosuccinic Acid or N-acetylcysteine
TL;DR: Results suggest that lead-induced oxidative stress in vivo can be mitigated by pharmacologic interventions, which encompass both chelating as well as thiol-mediated antioxidant functions.
About: This article is published in Free Radical Biology and Medicine.The article was published on 1996-01-01. It has received 172 citations till now. The article focuses on the topics: Glutathione & Antioxidant.
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TL;DR: This review examines the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.
Abstract: Reactive oxygen intermediates are produced in all aerobic organisms during respiration and exist in the cell in a balance with biochemical antioxidants. Excess reactive oxygen resulting from exposure to environmental oxidants, toxicants, and heavy metals perturbs cellular redox balance and disrupts normal biological functions. The resulting imbalance may be detrimental to the organism and contribute to the pathogenesis of disease and aging. To counteract the oxidant effects and to restore a state of redox balance, cells must reset critical homeostatic parameters. Changes associated with oxidative damage and with restoration of cellular homeostasis often lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant defense enzymes, and structural proteins. In this review, we examine the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.
1,075 citations
TL;DR: This review provides an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.
Abstract: Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.
765 citations
Cites background from "In vivo indices of oxidative stress..."
...[148] indicated that lead induced oxidative stress responded moderately to the treatment with DMSA accompanied by reduction in lead concentration from blood and soft tissue....
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01 Jan 2000
TL;DR: In this paper, the importance of using antioxidants in treating lead poisoning was discussed, and the possible protective effects of antioxidants in lead toxicity were investigated. But, the authors did not consider the effect of antioxidant supplementation following lead exposure.
Abstract: Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species, reducing the antioxidant defense system of cells via depleting glutathione, inhibiting sulfhydryl-dependent enzymes, interfering with some essential metals needed for antioxidant enzyme activities, and/or increasing susceptibility of cells to oxidative attack by altering the membrane integrity and fatty acid composition. Consequently, it is plausible that impaired oxidant/antioxidant balance can be partially responsible for the toxic effects of lead. Where enhanced oxidative stress contributes to lead-induced toxicity, restoration of a cell's antioxidant capacity appears to provide a partial remedy. Several studies are underway to determine the effect of antioxidant supplementation following lead exposure. Data suggest that antioxidants may play an important role in abating some hazards of lead. To explain the importance of using antioxidants in treating lead poisoning the following topics are addressed: (i) Oxidative damage caused by lead poisoning; (ii) conventional treatment of lead poisoning and its side effects; and (iii) possible protective effects of antioxidants in lead toxicity.
536 citations
TL;DR: Data suggest that antioxidants may play an important role in abating some hazards of lead, and that restoration of a cell's antioxidant capacity appears to provide a partial remedy.
524 citations
Cites background from "In vivo indices of oxidative stress..."
...Therefore captopril’s multiple benefits as an antioxidant and antihypertensive agent deserve to be explored to elucidate whether antioxidant effect of captopril can be a possible alternative mechanism for its known antihypertensive effect....
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TL;DR: The data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.
474 citations
References
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TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
225,085 citations
TL;DR: A modified HPLC procedure for the determination of MDA as the TBA-MDA complex is proposed, based on observations made of the conventional spectrophotometric procedure and three published high performance liquid chromatographic procedures.
783 citations
TL;DR: The hypothesis that lead impairs children's IQ at low dose is strongly supported by this quantitative review, and the effect is robust to the impact of any single study.
Abstract: We identified 24 modern studies of childhood exposures to lead in relation to IQ. From this population, 12 that employed multiple regression analysis with IQ as the dependent variable and lead as the main effect and that controlled for nonlead covariates were selected for a quantitative, integrated review or metaanalysis. The studies were grouped according to type of tissue analyzed for lead. There were 7 blood and 5 tooth lead studies. Within each group, we obtained jointPvalues by two different methods and average effect sizes as measured by the partial correlation coefficients. We also investigated the sensitivity of the results to any single study. The sample sizes ranged from 75 to 724. The sign of the regression coefficient for lead was negative in 11 of 12 studies. The negative partial r's for lead ranged from —.27 to —.003. The power to find an effect was limited, below 0.6 in 7 of 12 studies. The jointPvalues for the blood lead studies were (JAMA. 1990;263:673-678)
619 citations
TL;DR: In a cohort of 170 middle and upper-middle class children participating in a prospective study of child development and low-level lead exposure, higher blood lead levels at age 24 months were associated with lower scores at age 57 months on the McCarthy Scales of Children's Abilities.
Abstract: In a cohort of 170 middle and upper-middle class children participating in a prospective study of child development and low-level lead exposure, higher blood lead levels at age 24 months were associated with lower scores at age 57 months on the McCarthy Scales of Children's Abilities. The mean blood lead level at age 24 months was 6.8 micrograms/dL (SD = 6.3; 75th, 90th, and 99th percentiles: 8.8, 13.7, 23.6, respectively) and for all but 1 child was less than 25 micrograms/dL, the current definition of an "elevated" level. After adjustment for confounding, scores on the General Cognitive Index decreased approximately 3 points (SE = 1.4) for each natural log unit increase in 24-month blood lead level. The inverse association between lead level and performance was especially prominent for visual-spatial and visual-motor integration skills. Higher prenatal exposures were not associated with lower scores at 57 months except in the subgroup of children with "high" concurrent blood lead levels (ie, greater than or equal to 10 micrograms/dL). The concentration of lead in the dentine of shed deciduous teeth was not significantly associated with children's performance after adjustment for confounding.
413 citations
TL;DR: Whether the reaction be enzymic or nonenzymic, conjugation with GSH is a very important means of detoxication accounting in some cases for up to 60% of the biliary metabolites.
Abstract: Glutathione (GSH) is a strong nucleophile which reacts well with soft electrophiles, but poorly with both weak and strong electrophiles. Weak electrophiles have low reactivity with all nucleophiles...
378 citations