ROS scavenger, N-acetyl-l-cysteine and NOX specific inhibitor, VAS2870 reduce platelets apoptosis while enhancing their viability during storage

Transfusion. 2019 Apr;59(4):1333-1343. doi: 10.1111/trf.15114. Epub 2019 Jan 4.

Abstract

Background: Platelet storage is often complicated by deleterious changes that are started by reversible activation of the cells and can lead to procoagulant function and apoptosis during longer periods of storage. Given that increasing levels of reactive oxygen species (ROS) generation are associated with platelet activation and apoptosis, our study investigated whether ROS scavenging or the inhibition of ROS production can enhance the viability of stored platelets.

Methods: For this study platelet-rich plasma platelet concentrates (PRP-PCs) were either treated with ROS-reducing agents (1 mM N-acetyl-L -cysteine [NAC] or 30 μM NADPH oxidase [NOX] inhibitor, VAS2870) or kept untreated during storage. P-selectin expression, phosphatidylserine (PS) exposure, levels of microparticle (MP) formation, and intraplatelet caspase activity of PCs were analyzed by flow cytometry during 7 days of storage while the platelet viability was also evaluated by MTT assay.

Results: Both NAC- and VAS2870-treated platelets had significantly lower caspase activity, MP formation, and PS exposure during storage while they also showed improved viability. The platelet count and mean platelet volume (MPV) were also better preserved in the presence of NAC.

Conclusion: Our results confirmed that either the inhibition of ROS generation or the scavenging of these oxidant agents can attenuate platelet apoptosis while improving their viability during storage. In this study, the significant improvement of platelet viability obtained by NAC suggested that its supplementation with a designated safe concentration into PCs may better preserve the quality of these products, especially for longer storage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Apoptosis / drug effects*
  • Benzoxazoles / pharmacology*
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • Blood Preservation*
  • Cell Survival / drug effects
  • Free Radical Scavengers / pharmacology*
  • Humans
  • NADPH Oxidases / antagonists & inhibitors*
  • NADPH Oxidases / metabolism
  • Time Factors
  • Triazoles / pharmacology*

Substances

  • 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine
  • Benzoxazoles
  • Free Radical Scavengers
  • Triazoles
  • NADPH Oxidases
  • Acetylcysteine