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      The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate Translated title: Estado de maturação do nervo auditivo e tronco encefálico em ratos expostos a acetato de chumbo e suplementados com sulfato ferroso

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          Abstract

          Introduction:

          The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood.

          Objective:

          To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate.

          Methods:

          30 weanling male rats ( Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20 mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry.

          Results:

          We verified that the concentration of Pb in blood and in brainstem presented a high correlation ( r = 0.951; p < 0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100 mg/L), but not for the group exposed to the higher concentration (400 mg/L).

          Conclusion:

          This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect.

          Resumo

          Introdução:

          A literatura relatou a associação entre o chumbo e os efeitos auditivos, com base em estudos clínicos e experimentais. No entanto, não há consenso em relação aos efeitos do chumbo no sistema auditivo, ou sua correlação com a concentrção do metal no sangue.

          Objetivo:

          Investigar o estado de maturação do sistema auditivo, especificamente do nervo auditivo e do tronco encefálico, em ratos expostos ao acetato de chumbo e suplementados com sulfato ferroso.

          Método:

          30 ratos machos desmamados ( Rattus norvegicus, Wistar) foram distribuídos em seis grupos de cinco animais e expostos a urna de duas concentrações de acetato de chumbo (100 ou 400mg/L) e suplementados com sulfato ferroso (20mg/kg). O estado de maturação do nervo auditivo e do tronco encefálico foi analisado pelo Potencial Evocado Auditivo do Tronco Encefálico antes e após a exposição ao chumbo. A concentração de chumbo no sangue e tronco encefálico foi analisada utilizando-se Espectrometria de Massa com Plasma Indutivamente Acoplado.

          Resultados:

          Verificamos que as concentraçães de Pb no sangue e no tronco encefálico apresentaram alta correlação ( r = 0.951, p < 0.0001). Ambas as concentraçõs de acetato de chumbo afetaram o estado de maturação do sistema auditivo, sendo a maturação mais lenta nas regiões correspondentes á porção do nervo auditivo (onda I) e núcleos cocleares (onda II). A suplementação com sulfato ferroso reduziu significativamente a concentração de chumbo no sangue e tronco cerebral no grupo exposto á menor concentração de chumbo (100 mg/L), mas não para o grupo exposto á maior concentração (400 mg/L).

          Conclusão:

          Esse estudo indica que o acetato de chumbo pode ter efeitos deletérios na maturação do nervo auditivo e do tronco encefálico (região do núcleo coclear), como detectado pelos potenciais evocados auditivos do tronco encefálico, e que o sulfato ferroso pode diminuir parcialmente esse efeito.

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          Most cited references62

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          Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure

          Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.
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            Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease.

            We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'.
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              Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders.

              Trace metals such as iron, copper, zinc, manganese, and cobalt are essential cofactors for many cellular enzymes. Extensive research on iron, the most abundant transition metal in biology, has contributed to an increased understanding of the molecular machinery involved in maintaining its homeostasis in mammalian peripheral tissues. However, the cellular and intercellular iron transport mechanisms in the central nervous system (CNS) are still poorly understood. Accumulating evidence suggests that impaired iron metabolism is an initial cause of neurodegeneration, and several common genetic and sporadic neurodegenerative disorders have been proposed to be associated with dysregulated CNS iron homeostasis. This review aims to provide a summary of the molecular mechanisms of brain iron transport. Our discussion is focused on iron transport across endothelial cells of the blood-brain barrier and within the neuro- and glial-vascular units of the brain, with the aim of revealing novel therapeutic targets for neurodegenerative and CNS disorders.
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                Author and article information

                Journal
                101207337
                32669
                Braz J Otorhinolaryngol
                Braz J Otorhinolaryngol
                Brazilian journal of otorhinolaryngology
                1808-8694
                1808-8686
                21 October 2021
                23 January 2017
                Mar-Apr 2018
                12 November 2021
                : 84
                : 2
                : 150-158
                Affiliations
                [a ]Universidade de São Paulo (USP), Faculdade de Odontologia de Bauru, Bauru, SP, Brazil
                [b ]National Institute for Occupational Safety and Health (NIOSH), Atlanta, USA
                [c ]Universidade de São Paulo (USP), Faculdade de Odontologia de Bauru, Departamento de Fonoaudiologia, Bauru, SP, Brazil
                [d ]Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Departamento de Engenharia de Produção, Bauru, SP, Brazil
                Author notes
                [* ]Corresponding author. fernandazucki@ 123456hotmail.com (F. Zucki).
                Article
                HHSPA1749881
                10.1016/j.bjorl.2016.12.004
                8588627
                28209442
                bc809a42-a564-4c24-a92f-278a7b573e7c

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

                History
                Categories
                Article

                hearing,auditory evoked potentials,lead acetate,blood lead levels,ferrous sulfate,audição,potenciais evocados auditivos,acetato de chumbo,níveis de chumbo no sangue,sulfato ferroso

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