Gadolinium-based contrast agents suppress adipocyte differentiation in 3T3-L1 cells

Toxicol Lett. 2023 Jul 1:383:196-203. doi: 10.1016/j.toxlet.2023.07.003. Epub 2023 Jul 10.

Abstract

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to improve the sensitivity and enhance diagnostic performance. GBCAs are mostly eliminated from the body through the kidney after administration; however small amounts of gadolinium are retained in the brain and other tissues. Although there is increasing concern about the adverse health effects of gadolinium, the cellular effects of GBCAs remains poorly understood. Here, we elucidated the potential cytotoxicity of the GBCAs Omniscan and Gadovist in 12 different cell lines, especially 3T3-L1 adipocyte cell line. Omniscan and Gadovist treatments significantly increased intracellular gadolinium levels in 3T3-L1 cells in a time- and dose-dependent manner. Additionally, Omniscan and Gadovist treatments downregulated the expression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor γ (PPARG), adiponectin (ADIPOQ), and fatty acid-binding protein (FABP4), in 3T3-L1 cells, especially during early differentiation (day 0-2). Moreover, histological analysis using Oil red O staining showed that gadolinium chloride (GdCl3) treatment suppressed lipid droplet accumulation and the expression of adipocyte differentiation markers. Overall, the results showed that Omniscan and Gadovist treatment suppressed adipocyte differentiation in 3T3-L1 cells, contributing to the understanding of the potential toxic effects of GBCA exposure.

Keywords: 3T3-L1 cells; Adipocyte differentiation; Gadolinium chloride (GdCl(3)); Gadolinium-based contrast agents (GBCAs).

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes
  • Adipogenesis
  • Animals
  • Cell Differentiation
  • Contrast Media* / toxicity
  • Gadolinium* / toxicity
  • Magnetic Resonance Imaging
  • Mice
  • PPAR gamma / metabolism

Substances

  • Contrast Media
  • gadodiamide
  • gadobutrol
  • Gadolinium
  • PPAR gamma