Toxico-pathological effects of meglumine antimoniate on human umbilical vein endothelial cells

Toxicol In Vitro. 2019 Apr:56:10-18. doi: 10.1016/j.tiv.2018.12.018. Epub 2018 Dec 30.

Abstract

Leishmaniasis is one of the most important parasitic diseases after malaria. The standard treatment of leishmaniasis includes pentavalent antimonials (SbV); however, these drugs are associated with serious adverse effects. There have been very few studies pertaining to their side effects and mechanism of action in the fetus. This investigation examines the effects of meglumine antimoniate (MA) on the survival rate, angiogenesis and cellular apoptosis in the human umbilical vein endothelial cells (HUVECs). HUVECs were treated with varying doses of MA (100-800 μg/ml) for 24, 48 and 72 h and the survival rate was studied by colorimetric assay, flow cytometry, immunocytochemistry, migration (scratch) assay and tube formation assay. The results of quantitative real-time PCR (qPCR) studies indicated that the most important genes involved in presenting angiogenesis included VEGF and its receptors (Kdr and Flt-1), NP1 and Hif-1α genes including the anti-apoptotic gene of Bcl2, were significantly reduced compared to the control group (p < 0.05). In contrast, the most leading genes involved in the phenomenon of apoptosis were P53, Bax, Bak, Apaf-1 and caspases 3, 8 and 9, which were significantly up regulated compared to the control group (p < 0.05).

Keywords: Angiogenesis; Apoptosis; HUVECs; Meglumine antimoniate; Toxicity.

MeSH terms

  • Antiprotozoal Agents / toxicity*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • C-Reactive Protein / genetics
  • Cell Movement / drug effects
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Meglumine Antimoniate / toxicity*
  • Neovascularization, Physiologic / drug effects
  • Nerve Tissue Proteins / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antiprotozoal Agents
  • Apoptosis Regulatory Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nerve Tissue Proteins
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • neuronal pentraxin
  • Meglumine Antimoniate
  • C-Reactive Protein