In vitro evaluation of the toxicity of bismuth compounds

• Autor(a) principal: Gonçalves, Ângela Inês Lima
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/6268
• topic: Bismuto; Citotoxicidade; Cultura Celular; Viabilidade Celular Citometria de Fluxo; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Bismuth belongs to the group of heavy metals and shows a similar chemical behavior to arsenic and antimony; but unlike these it has been regarded as relatively nontoxic mainly due to its relatively low solubility in aqueous fluids. In contrast to the comprehensive database of other stable elements in the periodic table, bismuth has, perhaps, the least well established data bank, although it has long been used in medicine. In fact, bismuth salts are used to treat peptic ulcers, functional dyspepsia and chronic gastritis. In spite of the low available information, it is known that bismuth toxicity may be observed due to excessive ingestion, or misuse when taken in large quantities and for a long period of time. The reported toxic effects caused by an overdose of bismuth compounds include encephalopathy, nephropathy, osteoarthropathy, gingivostomatitis and colitis. As recently some clinical cases of bismuth toxicity have been described, our aim was to evaluate the toxicity of bismuth compounds commonly used in therapy and as catalysts in organic transformations. For this, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro cell proliferation effects of these compounds in representative cell lines such as neuronal (N27), intestinal (Caco-2), hepatic (HepaRG), breast (MCF-7) and in dermal fibroblasts (NHDF) were evaluated; it was observed that bismuth (III) trifluoromethanesulfonate and bismuth subnitrate led to a significant reduction of the proliferation of the neuronal cell line after 48h of exposition to the compounds. In addition, flow cytometry studies with propidium iodide staining and the 2’,7’ –dichlorofluorescein diacetate (DCFDA) assay, acellular reactive oxygen species detection assay) were performed intending to elucidate the potential mechanisms of cell death mediated by these compounds. The flow cytometry studies showed indeed some statistically significant cell death, but not in a great extent. These results are congruent with the DCFDA assay studies, which detected some oxidative stress, but again, not in a pronounced extent.