PUBLICATION

Cladribine inhibits a diltiazem-induced increase in red blood cell purine nucleotide concentrations in a zebrafish model

Authors
Klein, L.C., Yeung, P.K., and Berman, J.N.
ID
ZDB-PUB-091221-2
Date
2009
Source
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals   14(8): 554-559 (Journal)
Registered Authors
Berman, Jason
Keywords
none
MeSH Terms
  • Adenosine Triphosphate/blood
  • Animals
  • Biomarkers/blood*
  • Chromatography, High Pressure Liquid
  • Cladribine/therapeutic use*
  • Diltiazem/antagonists & inhibitors*
  • Diltiazem/pharmacology
  • Drug Interactions
  • Erythrocytes/drug effects*
  • Models, Animal
  • Pilot Projects
  • Purine Nucleotides/blood*
  • Zebrafish
PubMed
20001707 Full text @ Biomarkers
Abstract
Minimizing drug interactions is paramount to improving the efficacy and tolerability of cancer therapy. The zebrafish represents an innovative cancer model due to highly conserved genetics and inherent capacity for high-throughput chemical screening. This pilot study extends the utility of the zebrafish to a preclinical model for pharmacodynamics by examining the interaction of the nucleoside analogue, cladribine with the calcium channel blocker, diltiazem. Cladribine (0.7-3.5 mM) and/or diltiazem (2.4 mM), was injected intraperitoneally into adult zebrafish and red blood cell (RBC) lysates were assayed by HPLC for levels of purine nucleotides (e.g. ATP), potential biomarkers of cardiovascular health. Diltiazem increased RBC ATP concentrations, which were inhibited by co-injection of cladribine. These results suggest a novel drug interaction and highlight the feasibility of the zebrafish as an in vivo model for pharmacodynamic studies.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes