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
-
- Erythrocytes/drug effects*
- Animals
- Zebrafish
- Chromatography, High Pressure Liquid
- Cladribine/therapeutic use*
- Drug Interactions
- Models, Animal
- Biomarkers/blood*
- Diltiazem/antagonists & inhibitors*
- Diltiazem/pharmacology
- Adenosine Triphosphate/blood
- Purine Nucleotides/blood*
- Pilot Projects
- PubMed
- 20001707 Full text @ Biomarkers
Citation
Klein, L.C., Yeung, P.K., and Berman, J.N. (2009) Cladribine inhibits a diltiazem-induced increase in red blood cell purine nucleotide concentrations in a zebrafish model. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 14(8):554-559.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping