Cellular and Molecular Pathways Underlying the Nephrotoxicity of Gadolinium

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Sousa, NR (Autor) Outra; Rocha, S (Autor) Outra; Alice Santos Silva (Autor) FFUP; Coimbra, S (Autor) Outra; Valente, MJ (Autor) Outra

Revista

Título: Toxicological Sciences

Vol. 186

Páginas: 134-148

ISSN: 1096-6080

Editora: Oxford University Press

Indexação

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Outras Informações

ID Authenticus: P-00V-T11

DOI: 10.1093/toxsci/kfab148

Abstract (EN): Mounting evidence on the short- and long-term adverse effects associated with gadolinium [Gd (III)]-based contrast agents used in magnetic resonance imaging have emerged in the past 3 decades. Safety issues arise from the release of Gd (III) from chelates and its deposition in tissues, which is exacerbated in patients with renal disease, because the kidney is the major excretion organ of most of these agents. This study aimed at unveiling the cellular and molecular mechanisms of nephrotoxicity of Gd (III), using an in vitro model of human proximal tubular cells (HK-2 cell line). Cell viability declined in a concentration- and time-dependent manner after exposure to GdCl3 center dot 6H(2)O. The estimated inhibitory concentrations (ICs) eliciting 1%-50% of cell death, after 24 h of exposure, ranged from 3.4 to 340.5 mu M. At toxic concentrations, exposure to Gd (III) led to disruption of the oxidative status, mitochondrial dysfunction, cell death by apoptosis, switching to necrosis at higher levels, and autophagic activation. Disturbance of the lipid metabolism was already observed at low-toxicity ICs, with accumulation of lipid droplets, and upregulation of genes related to both lipogenesis and lipolysis. Gd (III)-exposure, even at the subtoxic IC01, increased the expression of modulators of various signaling pathways involved in the development and progression of renal disease, including inflammation, hypoxia, and fibrosis. Our results give new insights into the mechanisms underlying the nephrotoxic potential of Gd (III) and highlight the need to further clarify the risks versus benefits of the Gd (III)-based contrast agents currently in use.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15