In vitro effect of aspartame in angiogenesis induction

Renata Alleva, Battista Borghi, Lory Santarelli, Elisabetta Strafella, Damiano Carbonari, Massimo Bracci, Marco Tomasetti

Research output: Contribution to journalArticle

Abstract

Aspartame (APM) is the most widely used artificial sweetener and is added to a wide variety of foods, beverages, drugs, and hygiene products. In vitro and in vivo tests have reported contradictory data about APM genotoxicity. We evaluated the angiogenic effect of APM in an in vitro model using blood vessel development assay (Angio-Kit), cultured endothelial cells and fibroblasts. The release of IL-6, VEGF-A, and their soluble receptors sIL-R6 and sVEGFR-2 were determined over time in the conditioned medium of the Angio-Kit system, endothelial cells and cell lines with fibroblast properties after APM treatment. Reactive oxygen species (ROS) formation, cell viability, and stimulation of the extracellular signal-regulated kinases (erk1/2) and protein p38 were also evaluated. Exposure to APM induced blood vessel formation. ROS production was observed in endothelial cells after APM treatment, which was associated with a slight cell cytotoxicity. Neither intracellular ROS formation nor cell death was observed in fibroblasts. APM increases the levels of inflammatory mediator IL-6, VEGF and their soluble receptors released from endothelial cells into the medium. APM treatment induces VEGF-pathway activation by erk1/2 and p38 phosphorylation. APM at low doses is an angiogenic agent that induces regenerative cytokine production leading to the activation of MAPKs and resulting in the formation of new blood vessels.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalToxicology in Vitro
Volume25
Issue number1
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Aspartame
Endothelial cells
Blood vessels
Fibroblasts
Endothelial Cells
Vascular Endothelial Growth Factor A
Blood Vessels
Reactive Oxygen Species
Interleukin-6
Chemical activation
Cells
In Vitro Techniques
Sweetening Agents
Food and Beverages
Phosphorylation
Beverages
Mitogen-Activated Protein Kinase 1
Cell death
Cytotoxicity
Conditioned Culture Medium

Keywords

  • Angiogenesis
  • Aspartame
  • Genotoxicity
  • IL-6
  • ROS
  • VEGF

ASJC Scopus subject areas

  • Toxicology

Cite this

Alleva, R., Borghi, B., Santarelli, L., Strafella, E., Carbonari, D., Bracci, M., & Tomasetti, M. (2011). In vitro effect of aspartame in angiogenesis induction. Toxicology in Vitro, 25(1), 286-293. https://doi.org/10.1016/j.tiv.2010.09.002

In vitro effect of aspartame in angiogenesis induction. / Alleva, Renata; Borghi, Battista; Santarelli, Lory; Strafella, Elisabetta; Carbonari, Damiano; Bracci, Massimo; Tomasetti, Marco.

In: Toxicology in Vitro, Vol. 25, No. 1, 02.2011, p. 286-293.

Research output: Contribution to journalArticle

Alleva, R, Borghi, B, Santarelli, L, Strafella, E, Carbonari, D, Bracci, M & Tomasetti, M 2011, 'In vitro effect of aspartame in angiogenesis induction', Toxicology in Vitro, vol. 25, no. 1, pp. 286-293. https://doi.org/10.1016/j.tiv.2010.09.002
Alleva R, Borghi B, Santarelli L, Strafella E, Carbonari D, Bracci M et al. In vitro effect of aspartame in angiogenesis induction. Toxicology in Vitro. 2011 Feb;25(1):286-293. https://doi.org/10.1016/j.tiv.2010.09.002
Alleva, Renata ; Borghi, Battista ; Santarelli, Lory ; Strafella, Elisabetta ; Carbonari, Damiano ; Bracci, Massimo ; Tomasetti, Marco. / In vitro effect of aspartame in angiogenesis induction. In: Toxicology in Vitro. 2011 ; Vol. 25, No. 1. pp. 286-293.
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