NDLI: NT-proBNP as a biomarker for the assessment of a potential cardiovascular drug-induced liability in beagle dogs

Content Provider	Springer Nature Link
Author	Crivellente, Federica Tontodonati, Marcello Fasdelli, Nicola Casartelli, Alessandro Dorigatti, Roberto Faustinelli, Ivo Cristofori, Patrizia
Copyright Year	2011
Abstract	The amino-terminal pro-brain natriuretic peptide (NT-proBNP) is released into the plasma predominantly from ventricular cardiomyocytes, particularly in patients with chronic cardiac diseases, although small amounts are detectable in the plasma of healthy subjects. While NT-proBNP has been widely exploited in human medicine, limited literature is available related to its characterization in veterinary medicine (e.g., correlation with damage and specificity) and, particularly, in the context of preclinical drug safety assessment. This paper describes the analytical performance characteristics and the biological variability of NT-proBNP in male beagle dogs by using a commercially available enzyme-linked immunosorbent assay. Male beagle dogs were treated with Casopitant, an NK1 receptor antagonist under development for depression and anxiety, which, when administered chronically to dogs, caused cardiac toxicity. Heart weight increase, myocardial necrosis, degeneration, and inflammation associated with high serum levels of cardiac troponin I characterized the end stage pathology observed in dogs treated orally at 40 mg/kg for 39 weeks. Based on these data, ad hoc studies were designed in order to evaluate the possible relationship between NT-proBNP serum levels and both standard toxicology endpoints, such as the organ weight and histology, as well as nonstandard endpoints such as macroscopic morphometry and echocardiography. Early changes of NT-proBNP serum levels were observed following 2 weeks of treatment onward, preceding most, if not all of the anatomical and functional changes. The results obtained demonstrate that NT-proBNP acts as an early biomarker of cardiac changes, representing a sensitive and predictive marker of drug-induced cardiac liability.
Starting Page	425
Ending Page	438
Page Count	14
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	27
Issue Number	6
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-08-08
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Biomarker Dog Heart toxicity Hypertrophy NT-proBNP Biochemistry Cell Biology Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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