Prilocaine hydrochloride protects zebrafish from lethal effects of ionizing radiation: Role of hematopoietic cell expansion

Manali Dimri, Jayadev Joshi, Nitisha Shrivastava, Subhajit Ghosh, Rina Chakraborti, Prem Kumar Indracanti

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Drug repositioning is an approach of significant translatability, and the present study was undertaken to screen a collection of FDA approved small-molecule clinical compounds for identification of novel radioprotective agents. Screening of JHCCL (Johns Hopkins Clinical Compound Library), a collection of 1,400 FDA approved small molecules, lead to identification of prilocaine hydrochloride, a local anesthetic used widely during dental procedures, as a potential radioprotector. Prilocaine, at a concentration of 20 μM, protected zebrafish from radiation induced (20 Gy) pericardial edema (PE), microphthalmia and rendered 60 % survival advantage over radiation exposed controls. While 40 % survival advantage over radiation exposed controls was achieved with 10 μM prilocaine. Prilocaine, in a dose-dependent manner, scavenged, radiation-induced hydroxyl radicals and maximally (43 %) at the highest concentration (1 mM) tried in this study. However, prilocaine exerted a mild superoxide anion scavenging potential (around 5 %) at all the concentrations used within this study. Prilocaine, at 20 μM concentration, significantly increased erythropoiesis, a marker for HSC function, in caudal hematopoietic tissue (CHT) in wild type and anemic zebrafish embryos (1.48 and 0.85 folds respectively) when compared to untreated (1) and phenylhydrazine (PHZ) (0.41 fold) treated control groups respectively. These results suggest that prilocaine is a radioprotective agent and free radical scavenging and HSC expanding potential seems to be contributing towards its radioprotective action.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalTokai Journal of Experimental and Clinical Medicine
Volume40
Issue number1
StatePublished - Apr 2014
Externally publishedYes

Keywords

  • Beta blocker
  • Drug repurposing
  • Hematopoietic stem cells
  • Radioprotection
  • Zebrafish

ASJC Scopus subject areas

  • Medicine(all)

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