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      Efectos de la N-Acetilcisteína y Metionina en intoxicación aguda con plomo en ratas wistar

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          Abstract

          El Plomo es un elemento ubicuo en el ambiente. El estrés oxidativo es considerado un mecanismo por el cual causa toxicidad. La finalidad de este trabajo fue determinar el efecto de la N-Acetilcisteina y Metionina en la intoxicación con Plomo, sobre los niveles sanguíneos de Plomo, Hematocrito (Hto), ALA-D y niveles de malondialdehido (MDA) en hígado y riñón. Se utilizaron 60 ratas Wistar, con peso promedio de 185 g. dividas en cinco grupos. Grupo 1, el Control, se determinaron niveles básales, el Grupo 2 de Intoxicación, los grupos restantes una vez intoxicados recibieron tratamiento de la forma siguiente Grupo 3 N-Acetilcisteína (NAC), Grupo 4 Metionina (MET), Grupo 5 NAC + MET. Los resultados mostraron que la NAC disminuye los niveles de plomo en sangre en un 23% (p< 0.05), aumenta el Hto y la actividad del la ALA-D. La combinación NAC+MET disminuye los niveles de plomo en sangre en un 41% (p<0.001) con un aumento del Hto (p<0.05) y aumento de la actividad de ALA-D en un 16% (p<0.001). En relación al MDA en hígado y riñón, la NAC disminuye los niveles de MDA en hígado en un 29% (p<0.05). El tratamiento NAC+MET induce a un aumento significativo estadísticamente de MDA en hígado y disminución en riñón. En esta investigación se puede concluir que la NAC muestra un efecto quelante débil sobre los niveles plasmáticos de plomo y revierte las alteraciones a nivel de parámetros sanguíneos estudiados, además revierte la peroxidación lípidica a nivel hepático. La combinación NAC + MET tiene un comportamiento dual, a nivel hepático es prooxidante y a nivel renal antioxidante.

          Translated abstract

          Lead is a ubiquitous element in the environment. Oxidative stress is considered a mechanism which causes toxicity. The objective of this work is to determine the effect of N-Acetylcyteine and Methionine on lead poisoning in blood levels for lead, hematocrit, ALA-D and levels of malondialdehide (MDA) in the liver and kidneys. Sixty Wistar rats with an average weight of 185 g. were used. They were divided into five groups. In Group 1, the control, basal levels were determined, in Group 2, intoxication and in the rest of the groups, once intoxicated, they received treatment in the following manner: Group 3, N-Acetylcyteine (NAC). Group 4 Methionine (MET) and Group 5 NAC + MET. Results showed that NAC lowers lead levels in the blood in 23% (p<0.05) increases hematocrit and ALA-D activity. The combination of NAC + MET lowers the levels of lead in the blood in 41% (p<0.001) with a hematocrit increase (p<0.05) and an increase in the ALA-D activity of 16% (p<0.001). With respect to the MDA in the liver and kidneys, NAC lowers the levels of MDA in the liver in 29% (p<0.05). The NAC +MET treatment induces a statistically significant MDA increase in the liver and a decrease in the kidney. In this research, it can be concluded that NAC shows a weak Chelate effect on the plasmatic levels of lead and reverts alteration at the level of the blood parameters studied in addition to reverting lipidic peroxidation at the hepatic level. The combination of NAC + MET has dual behavior, at the hepatic level it is pro-oxidant and at the renal level antioxidant.

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          Antioxidant effects of alpha tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats.

          Lead exposure related oxidative stress has been incriminated, at least in part, to its toxic effects in different organs. The present investigation was carried out to study the ameliorative effects of antioxidant (ascorbic acid, alpha tocopherol or L-methionine) alone and antioxidant (alpha tocopherol) plus a conventional chelator (CaNa2 EDTA) on some of the parameters indicative of oxidative stress in the liver, kidney and brain in lead-exposed rats. Rats were given 0 (n=6, healthy controls) or 1 mg of Pb(2+)/kg b.w (n=30) as lead acetate solution in sterile normal saline ip for a period of 4 weeks. The ip injections were then withdrawn and lead exposed rats were randomly divided into five equal groups. Six lead-exposed rats were given no treatment during the 5th week (Pb group) to serve as positive controls. The rest four groups received either ascorbic acid, alpha tocopherol or L-methionine in the 5th week at the daily dose of 100 mg/kg b.w orally or alpha tocopherol as above plus CaNa2 EDTA at the rate of 110 mg/kg b.w twice a day ip for a period of 4 days. All the animals were sacrificed 1 day after the end of the experiment, and the liver, kidney and brain were quickly excised for the estimation of lead burden and alteration in the oxidative indices. Lead exposure for a period of 4 weeks followed by a period of 1 week to recover, resulted in significantly (P<0.05) higher accumulation of lead, associated with significant (P<0.05) increases in lipid peroxide level in the liver and brain, and non-protein bound thiol contents in the brain. Changes in the superoxide dismutase and catalase activities in lead-exposed rats did not reach statistical (P<0.05) significance. Treatment with antioxidants alone resulted in reversal of oxidative stress without significant decline in tissue lead burden. Tissue specific changes, following lead exposure and responses to the treatment with different antioxidants were recorded in the parameters of oxidative damage viz. lipid peroxide level, antioxidant enzymes and thiol contents.
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            Can antioxidants be beneficial in the treatment of lead poisoning?

            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.
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              Lead-induced regional lipid peroxidation in brain.

              Rats exposed to lead (2% lead acetate in drinking water for a period of 10 days) showed altered levels of phospholipids, lipid peroxide and lead ions. Lead ion concentrations were significantly increased in all brain regions with a maximum retention in the spinal cord and cerebellum. The cerebral cortex showed a higher percent elevation of lead ions as compared to the other areas of the brain. The phospholipid contents were significantly depressed in the cerebral cortex, cerebellum and spinal cord. Subsequently, the rate of lipid peroxidation has been enhanced in all brain regions following toxicosis. Increased rate of lipid peroxidation and decreased levels of phospholipids followed the similar rank order as that of increasing lead concentration was spinal cord, cerebellum, cerebral cortex and brain stem after lead intoxication.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                avft
                Archivos Venezolanos de Farmacología y Terapéutica
                AVFT
                Sociedad Venezolana de Farmacológia y Farmacológia Clínica y Terapéutica. Escuela de Medicina (Caracas )
                0798-0264
                June 2006
                : 25
                : 1
                : 33-38
                Affiliations
                [1 ] ULA
                [2 ] ULA
                [3 ] ULA
                [4 ] ULA
                [5 ] ULA
                Article
                S0798-02642006000100005
                c7877911-ae5e-4ec6-bb03-53bb6f2c0932

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Venezuela

                Self URI (journal page): http://www.scielo.org.ve/scielo.php?script=sci_serial&pid=0798-0264&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                lead poisoning,products reactive to thiobarbituric,N-Acetylcyteine (NAC),Methionine (MET),Intoxicación por Plomo,Productos reactivos al tiobarbiturico,Malondialdehido (MDA),N-Acetilcisteina (NAC),Metionina (MET)

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