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      Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats

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          Abstract

          The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

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          Determination of carbonyl content in oxidatively modified proteins.

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            Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage.

            Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals. In order to prove the importance of using antioxidants in heavy metal poisoning, pertinent biochemical mechanisms for metal-induced oxidative stress should be reviewed.
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              Structure-activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives.

              Gallic acid and its derivatives are a group of naturally occurring polyphenol antioxidants which have recently been shown to have potential healthy effects. In order to understand the relationship between the structures of gallic acid derivatives, their antioxidant activities, and neuroprotective effects, we examined their free radical scavenging effects in liposome and anti-apoptotic activities in human SH-SY5Y cell induced by 6-hydrodopamine autooxidation. It was found that these polyphenol antioxidants exhibited different hydrophobicity and could cross through the liposome membrane to react with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical in a time and dose-dependent manner. At the same time, the structure-antioxidant activity relationship of gallic acid derivatives on scavenging DPPH free radical in the liposome was also analyzed based on theoretical investigations. Analysis of cell apoptosis, intracellular GSH levels, production of ROS and the influx of Ca(2+) indicated that the protective effects of gallic acid derivatives in cell systems under oxidative stress depend on both their antioxidant capacities and hydrophobicity. However, the neuroprotective effects of gallic acid derivatives seem to depend more on their molecular polarities rather than antioxidant activities in the human SH-SY5Y cell line. In conclusion, these results reveal that compounds with high antioxidant activity and appropriate hydrophobicity are generally more effective in preventing the injury of oxidative stress in neurodegenerative diseases.
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                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                22 February 2016
                2016
                22 February 2016
                : 3
                : 351-356
                Affiliations
                [a ]Programa de Pós-Graduação em Farmacologia, Universidade de São Paulo (USP), SP, Brazil
                [b ]Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), RS, Brazil
                [c ]Universidade Federal da Fronteira Sul (UFFS), PR, Brazil
                [d ]Programa de Pós-Graduação em Bioquímica, UFSM, RS, Brazil
                [e ]Programa de Pós-Graduação em Química, UFSM, RS, Brazil
                [f ]Departamento de Química, UFSM, RS, Brazil
                [g ]Departamento de Fisiologia e Farmacologia, UFSM, RS, Brazil
                Author notes
                [* ]Corresponding author at: Universidade de São Paulo, Instituto de Ciências Biomédicas I, Avenida Professor Lineu Prestes 1524, Sala 317 Butantã, São Paulo, CEP 05508-000 SP, Brazil. reckziegel.patricia@ 123456gmail.com
                Article
                S2214-7500(16)30018-X
                10.1016/j.toxrep.2016.02.005
                5615824
                28959556
                4c873853-127c-4251-b638-d6fb4856e572
                © 2016 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 December 2015
                : 27 January 2016
                : 17 February 2016
                Categories
                Article

                antioxidant,chelating agent,gallic acid,lead,oxidative stress

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