Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/20949
Título: Antioxidants prevent the cytotoxicity of manganese in RBE4 cells
Autor: Marreilha dos Santos, A. P.
Santos, Dinamene
Au, Catherine
Milatovic, Dejan
Aschner, Michael
Batoreu, M. Camila C.
Palavras-chave: Neurosciences
Data: 2008
Editora: ELSEVIER SCIENCE BV
Citação: BRAIN RESEARCH. - Vol. 1236 (OCT 21 2008), p. 200-205
Resumo: Manganese (Mn) is an essential trace element required for ubiquitous enzymatic reactions. Chronic overexposure to this metal may, however, promote potent neurotoxic effects. The mechanism of Mn toxicity is not well established, but several studies indicate that oxidative stress and mitochondria play major roles in the Mn-induced neurodegenerative processes that lead to dysfunction in the basal ganglia. The aim of this study was to address the toxic effects of MnCl2 and MnSO4 on the immortalized rat brain microvessel endothelial cell line (RBE4) and to characterize toxic mechanism associated with exposure to Mn. The cytotoxicity of Mn in RBE4 cells was evaluated using the LDH and the MTT assays. A significant increase was noted in LDH release from RBE4 cells exposed for 24 h to MnCl2 at concentrations of 800 mu M and MnSO4 at concentrations = 400 mu M (p 0.05) when compared with control unexposed cells. The MTT assay established significant decrease in cellular viability upon exposure to MnCl2 at concentrations = 50 mu M (p 0.05). Thus, the cytotoxicity assays showed that the MTT assay was more sensitive than the LDH assay, suggesting that mitochondrial changes precede other toxic effects of Mn. In addition, upon exposure to MnCl2 (200 and 800 mu M), intracellular reduced glutathione (GSH) levels in RBE4 cells decreased as Mn exposure concentrations increased (p 0.05). To confirm the oxidative hypothesis of Mn cytotoxicity, co-exposure of MnCl2 with antioxidant agents (N-acetylcysteine [NAC] or Trolox) were carried out. The cellular viability was evaluated using the MTT assay. A significant decrease in Mn cytotoxicity was observed in co-exposed cells confirming that (1) oxidative stress plays a critical role in the mechanism of Mn toxicity, and (2) antioxidants may offer a useful therapeutic modality to reverse the aberrant effects of Mn. (C) 2008 Elsevier B.V. All rights reserved.. - NIEHS [10563]; DOD [W81XWH-05-1-0239]. - The authors gratefully acknowledge the mentorship and support of Professors Luisa Mateus, Isabel Almeida and Isabel Rivera. Partial support was provided by grants from NIEHS 10563 and DOD W81XWH-05-1-0239 (MA),
URI: http://hdl.handle.net/10451/20949
DOI: http://dx.doi.org/10.1016/j.brainres.2008.07.125
ISSN: 0006-8993
Aparece nas colecções:FF - Produção Científica 2000-2009

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