LONG-TERM EXPOSURE TO ALUMINUM AT EQUIVALENT URBAN REGION CONSUMPTION DOSE INDUCES OXIDATIVE STREESS AND PROTEOMIC MODULATION IN SPINAL CORD OF RATS
Author(s): Lima WF; Bittencourt LO; Aragão WAB; Mendes PF; Puty B; Dionizio A; Buzalaf MAB; Lima RR;
Presenter: Leonardo Oliveira Bittencourt
The aluminum (Al) is a neurotoxicant agent capable of triggering several neurotoxic damages, such as behavioral changes, neurodegenerative processes and neurochemical changes, and for that reason mechanisms of damage and safety concentrations are still subject of discussion. Nevertheless, the majority of studies uses models of acute exposure to non-representative doses to the human daily life. In addition to that, the evidences regarding the effects of Al exposure over the spinal cord, an important organ from central nervous system for somesthetic and motor functions. Thus, the purpose of this study was to investigate the effects of Al exposure at low doses for a long-period, representative of the human consumption in urban areas, on the global proteomic profile and oxidative biochemistry parameters in the spinal cord of adult rats. For this, twenty adults male Wistar rats (90 days of life) were divided into a control group (n=10) that received ultrapure water, and the exposed group (n=10) that received aluminum chloride (AlCl3 – dose 8.3 mg/kg/day) by intragastric gavage for 60 days, with weekly dose adjustment based on the body weight. After this period, the laminectomy was performed to remove the spinal cord, which was submitted to oxidative biochemistry and proteomic analyses. Label-free proteomic analysis was carried out in a nanoACQUITY UPLC System coupled to a mass spectrometer. The data was analyzed by Enrichment Term Analysis based on Gene Ontology in Cytoscape software, followed by the over-representation approach using R programing language. In the oxidative biochemistry analyses, the antioxidant capacity was evaluated by Reduced Glutathione (GSH) analysis and the prooxidant parameter of lipid peroxidation (LPO) by thiobarbituric acid reactive substances assay. The results were analyzed by Student’s t-test adopting p<0.05. The biochemical findings showed an oxidative stress status in spinal cord due to the reduction in GSH content and the increase in LPO levels in the group exposed to Al. Moreover, the proteomic approach showed changes in the status of regulation of 262 proteins associated with processes related to cell cycle, cytoskeleton regulation, stimulus response, neurological system regulation, protein activity and synaptic signaling. It was observed an intrinsic relationship between the proteome modulation and oxidative stress, by the modulation of ubiquitin-proteasome system and heat shock proteins. Besides that, the proteomic approach also suggested an imbalance on the energy metabolism, myelin sheath composition and cytoskeleton rearrangement. Therefore, these findings suggest that the antioxidant capacity failure culminated in the oxidative stress state. In addition to that, the Al exposure is also associated with the modulation of several proteins underlying the redox cellular system and proteome protection, that may drive to damages to proteins, lipids and DNA, which may lead to damages on spinal cord somesthetic and motor functions. This study was financed in part by the Programa Nacional de Cooperação Acadêmica na Amazônia – PROCAD/Amazônia from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - This research was also supported by Pró-Reitoria de Pesquisa da UFPA (PROPESP, UFPA, Brazil) and Brazilian National Council for Scientific and Technological Development (CNPq).
Keywords: Aluminum; Spinal Cord; Neurotoxicology
Graduada em Ciências Biológicas pela Universidade Federal de São Carlos (1985) com mestrado em Ciências (Fisiologia Geral) pela Universidade de São Paulo (1990). Realizou o doutorado no Departamento de Fisiologia Geral do IBUSP e no Departamento de Zoologia da Universidade de Leicester, Inglaterra e...Saiba mais
2000-Present Professor Aquatic Ecotoxicology, University of California, Riverside, CA USA
1995-1999 Associate Professor Pharmacology and Environmental Toxicology, University of Mississippi, MS USA
1991-1995 Assistant professor Pharmacology and Toxicology, University of Arkansas for Medi...
Gisela de Aragão Umbuzeiro is a full professor at School of Technology – UNICAMP, Brazil and an adjunct professor at Wilson College of Textiles, NCSU, USA. She graduated in Biology at University of Campinas - UNICAMP (1979), Ph.D. in Genetics also at UNICAMP (1990). Worked for 22 years at the Enviro...Saiba mais
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