Objective: Parstatin, the N-terminal 41-amino-acid peptide cleaved by thrombin from protease-activated-receptor 1, was shown to be highly effective in preventing ocular angiogenesis and as such it has potential therapeutic applications in ocular neovascular diseases. In the frame of a safety program in preclinical development, we investigated whether parstatin exerts any cytotoxic effect in critical ocular cell populations.
Materials And Methods: Human retinal pigment epithelium cell-19 line (ARPE-19) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay were used to investigate parstatin's effect in cell cultures. Parstatin 24-41 was used as a control peptide which lacks the hydrophobic domain to demonstrate the specificity and the structure-dependent effect of parstatin. Both peptides were used at concentrations ranging from 0.1-30 μM for 24, 48 and 72 hours.
Results: In the presence of parstatin the rate of ARPE-19 cell growth and viability were significantly decreased in a concentration-dependent and time-dependent manner, with an IC50 of approximately 10 μM. When ARPE-19 cells were treated with parstatin 24-41 no inhibitory effect was observed at any concentration or exposure time used.
Conclusions: Parstatin has a clear detrimental effect on the viability of ARPE-19 cells and raises concerns about its use in the eye because of its possible toxic effects.
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Parstatin inhibits viability of human retinal pigment epithelium cells: an in vitro cytotoxicity study.
Eur Rev Med Pharmacol Sci
May 2020
Department of Pathology, School of Medicine, University of Patras, Patras, Greece.
Objective: Parstatin, the N-terminal 41-amino-acid peptide cleaved by thrombin from protease-activated-receptor 1, was shown to be highly effective in preventing ocular angiogenesis and as such it has potential therapeutic applications in ocular neovascular diseases. In the frame of a safety program in preclinical development, we investigated whether parstatin exerts any cytotoxic effect in critical ocular cell populations.
Materials And Methods: Human retinal pigment epithelium cell-19 line (ARPE-19) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay were used to investigate parstatin's effect in cell cultures.
Combined Treatment With Exenatide and Cyclosporine A or Parstatin 1-26 Results in Enhanced Reduction of Infarct Size in a Rabbit Model.
J Cardiovasc Pharmacol
July 2017
*Department of Pharmacology, Medical School, University of Patras, Patras, Greece;†Department of Cardiothoracic Surgery, University Hospital of Patras, Patras, Greece; and‡Genesis Pharma S.A., Athens, Greece.
Exenatide and cyclosporine A have been shown to moderately protect against myocardial reperfusion injury leading to reduction of infarct size in patients. Our objective was to investigate whether the combined treatment with exenatide (glucagon-like peptide 1 receptor agonist) and cyclosporine A or parstatin 1-26 (inhibitors of mitochondrial permeability transition pore and/or inflammation) is more beneficial than either agent alone. Rabbits underwent 40 minutes of ischemia and 120 minutes of reperfusion.
View Article and Find Full Text PDFAnti-Parstatin Promotes Angiogenesis and Ameliorates Left Ventricular Dysfunction during Pressure Overload.
Int J Biomed Sci
March 2014
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY-40202, USA.
Unlabelled: Parstatin, a novel protease activated receptor-1 (PAR-1) derived peptide is a potent inhibitor of angiogenesis. We and others have reported that imbalance between angiogenic growth factors and anti-angiogenic factors results in transition from compensatory cardiac hypertrophy to heart failure in a pressure overload condition. Though cardio protective role of parstatin was shown previously in ischemic cardiac injury, its role in pressure overload cardiac injury is yet to unveil.
View Article and Find Full Text PDFInfluence of parstatin on experimental periodontal disease and repair in rats.
J Periodontol
September 2014
Department of Physiology and Pathology, Dental School at Araraquara, State University of São Paulo, Araraquara, São Paulo, Brazil.
Background: Parstatin is a 41-amino acid peptide, formed by proteolytic cleavage on activation of the protease activated receptor-1, with antiangiogenic properties. The purpose of this study is to evaluate the influence of synthetic parstatin on experimental periodontal disease and repair in rats.
Methods: Ligature-induced periodontitis was established in rats and the influence of parstatin administration was assessed after 8 and 15 days for periodontal disease and 24 hours and 8 days after repair after ligature removal.
Parstatin prevents renal injury following ischemia/reperfusion and radiocontrast administration.
Am J Nephrol
March 2013
Department of Radiology, Medical School, University of Patras, Rio-Patras, Greece.
Background/aims: Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the protease-activated receptor 1. Parstatin was recently found to be cardioprotective against myocardial ischemia/reperfusion (IR) injury. In the present study, it was hypothesized that parstatin would protect the kidneys in acute renal failure.
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