In vitro PAMAM, phosphorus and viologen-phosphorus dendrimers prevent rotenone-induced cell damage

Int J Pharm. 2014 Oct 20;474(1-2):42-9. doi: 10.1016/j.ijpharm.2014.08.010. Epub 2014 Aug 7.

Abstract

We have investigated whether polyamidoamine (PAMAM), phosphorus (pd) and viologen-phosphorus (vpd) dendrimers can prevent damage to embryonic mouse hippocampal cells (mHippoE-18) caused by rotenone, which is used as a pesticide, insecticide, and as a nonselective piscicide, that works by interfering with the electron transport chain in mitochondria. Several basic aspects, such as cell viability, production of reactive oxygen species and changes in mitochondrial transmembrane potential, were analyzed. mHippoE-18 cells were treated with these structurally different dendrimers at 0.1μM. A 1h incubation with dendrimers was followed by the addition of rotenone at 1μM, and a further 24h incubation. PAMAM, phosphorus and viologen-phosphorus dendrimers all increased cell viability (reduced cell death-data need to be compared with untreated controls). A lower level of reactive oxygen species and a favorable effect on mitochondrial system were found with PAMAM and viologen-phosphorus dendrimers. These results indicate reduced toxicity in the presence of dendrimers.

Keywords: Cytotoxicity; Dendrimers; Parkinson’s disease; Rotenone.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Dose-Response Relationship, Drug
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Molecular Structure
  • Phosphorus / chemistry
  • Phosphorus / pharmacology*
  • Polyamines / chemistry
  • Polyamines / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Rotenone / antagonists & inhibitors*
  • Rotenone / chemistry
  • Rotenone / pharmacology*
  • Structure-Activity Relationship
  • Viologens / pharmacology*

Substances

  • Dendrimers
  • Poly(amidoamine)
  • Polyamines
  • Reactive Oxygen Species
  • Viologens
  • Rotenone
  • Phosphorus