Attenuation of cadmium-induced vascular toxicity by pro-angiogenic nanorods

Mater Sci Eng C Mater Biol Appl. 2020 Oct:115:111108. doi: 10.1016/j.msec.2020.111108. Epub 2020 May 21.

Abstract

Cadmium (Cd) is a common heavy metal that causes major environmental pollution with adverse effects on human health and well-being. Exposure to Cd is known to exhibit detrimental consequences on all the vital organ systems of the body, especially the vascular system. Certain approaches using anti-oxidants and chelating agents have been demonstrated previously to mitigate Cd-induced toxicity. However, these approaches are associated with their own limitations. In this context, there is a critical need for the development of alternative treatment strategies to address the conditions associated with Cd-poisoning. One such novel approach is the application of nanomedicine which is well-known to resolve several health complications by improving disease therapy. Recently, our group demonstrated the role of europium hydroxide nanorods (EHN) in promoting vascular growth using in vitro and in vivo assay systems. Therefore, in the present study, we have evaluated the effect of EHN on health of endothelial cells (EA.hy926) and fibroblasts (NIH 3T3) intoxicated by Cd. The results revealed that EHN significantly improved the viability of EA.hy926 and NIH 3T3 cells, reduced apoptotic cell population, increased nitric oxide (NO) production and promoted blood vasculature development in the chick embryo model, which were hampered due to Cd insult. Molecular studies demonstrated the reduced expression of tumor suppressor (p53) and elevated anti-apoptotic protein (Bcl-xL) levels along with enhanced NO production through endothelial nitric oxide synthase (eNOS) activation as the plausible mechanisms underlying protective role of EHN against Cd-induced vascular toxicity. Considering the above observations, we strongly believe that EHN could be a potential nanomedicine approach for overcoming Cd-induced toxicity by improving vascular health and functioning.

Keywords: Apoptosis; Cadmium; Chick embryo angiogenesis; Europium hydroxide nanorods; Nitric oxide; Vascular toxicity.

MeSH terms

  • Angiogenesis Inducing Agents / chemistry
  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cadmium / toxicity*
  • Cell Line
  • Cell Survival
  • Chick Embryo
  • Embryo, Nonmammalian / blood supply*
  • Embryo, Nonmammalian / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Europium / chemistry
  • Europium / pharmacology*
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Nanotubes
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects

Substances

  • Angiogenesis Inducing Agents
  • Cadmium
  • Nitric Oxide
  • Europium