Dataset Information

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

ABSTRACT: There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

SUBMITTER: Kim K

PROVIDER: S-EPMC5330931 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

Kim Kyuri K Chini Naseem N Fairchild David G DG Engle Steven K SK Reagan William J WJ Summers Sandra D SD Mirsalis Jon C JC

Toxicologic pathology 20160928 8

There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natr ...[more]

PMID: 27638646

Similar Datasets

Project description:In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.

Dataset Information

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

Publications

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets