Cell viability of fibroblasts to pifenidone and sirolimus: a future concept for drug eluting stents

Int J Pharm. 2014 May 15;466(1-2):38-43. doi: 10.1016/j.ijpharm.2014.03.003. Epub 2014 Mar 5.

Abstract

Background: Currently one of the major problems that interventional pulmonologists have to face is the increased proliferation of fibrinous tissue on the site of the stent placement, and usually at the two ends.

Materials and methods: The drugs rapamycin and pirfenidone were chosen for our experiment. Fibroblasts were also cultured in order to administer pirfenidone and rapamycin in different concentrations. The following cell viability methods were used: (a) Senescence - Cell Titer Assay, (b) Necrosis - Cyto Tox Assay and (c) Apoptosis - Caspase-Glo 3/7 Assay.

Results: Rapamycin has minimal to no effect on fibroblasts regarding apoptosis, senescence and necrosis. 0.1 to 1 μM. Pirfenidone concentrations lead to an elevated cell metabolism because cells try to evade the cytotoxic effect of the drug. Increasing Pirfenidone concentrations lead to higher apoptosis rates. 10 μM pirfenidone induces the highest apoptosis rates in this experiment and reduce cell viability to a minimum.

Conclusion: Necrosis is unaffected by the investigated drugs.

Keywords: Everolimus; Everolimus (Pub Chem CID: 6442177); Paclitaxel (Pub Chem CID: 441276); Pirfenidone; Pirfenidone (Pub Chem CID: 40632); Rapamycin; Rapamycin (Pub Chem CID: 5284616); Zotarolimus; Zotarolimus (Pub Chem CID: 23375907).

MeSH terms

  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Drug-Eluting Stents*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • L-Lactate Dehydrogenase / metabolism
  • Pyridones / pharmacology*
  • Sirolimus / pharmacology*

Substances

  • Immunosuppressive Agents
  • Pyridones
  • pirfenidone
  • L-Lactate Dehydrogenase
  • Caspase 3
  • Caspase 7
  • Sirolimus